Therapeutic clay compositions and methods of using

ABSTRACT

The present invention provides methods of improve efficiency, growth, and performance in an animal by orally administering to the animal an effective amount of a therapeutic clay. The methods can reduce embryonic loss, increase litter size, increase the number of live births, improve the immune status of the maternal animal, reduce the concentration of maternal fecal amino acids, reduce the concentration of maternal fecal short-chained amino acid, increasing litter birth weight in the maternal animal, increase the amount of young animal colostrum intake, reduce young animal pre-weaning mortality, reduce the number of young animals lost due to low viability, reduce the number of weaned young animals, improve the immune status of young animals at weaning, reduce the number of lightweight young animals from nursery to market, increase the number of young animals marketed per sow, and increase calculated litter weight gain.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/855,600, filed May 31, 2019, the contents of all of which are herebyincorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention generally relates to methods of using therapeuticclay, formulations comprising therapeutic clay, and methods of improvingperformance of an animal using the therapeutic clay.

BACKGROUND OF THE INVENTION

A number of artificial growth promoters are used extensively to controlhealth challenges, enhance lean tissue gain, and improve growth,performance, and efficiency of feed utilization in livestock production.But use of artificial substances in livestock production has to becomeless prevalent as the market demands change. Therefore, the livestockindustry is in need of alternative technologies to manage their herdhealth and production efficiency through all livestock growth productionstages in the absence of artificial growth promoters. Optimally, thisalternative growth promoter would be easy to implement on-farm andprovide multiple benefits to herd health and production from birth tomarket.

SUMMARY OF THE INVENTION

One aspect of the disclosure encompasses a method of improvingreproductive and litter performance of a maternal animal. The methodcomprises orally administering to the animal an effective amount of atherapeutic clay. In some aspects, the animal is a pig.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning.

Improving reproductive performance can comprise reducing embryonic loss,increasing litter size, increasing the number of live births, improvingthe immune status of the maternal animal, reducing the concentration ofmaternal fecal amino acids, reducing the concentration of maternal fecalshort-chained amino acid, and increasing litter birth weight. Improvingthe immune status of the maternal animal can comprise an increased levelof IFNγ and TNF-α in the maternal animal, and decreased levels of TRAILin the maternal animal. In some aspects, the level of pre-farrowingTNF-α in the maternal animal is positively correlated with total wean,negatively correlated with subsequent stillborns, and positivelycorrelated with subsequent mummies. In some aspects, the level ofpre-farrowing TRAIL is negatively correlated with subsequent total bornand subsequent born alive. In some aspects, the level of wean IFN-γ ispositively correlated with total wean.

Improving litter performance can comprise increasing the amount of younganimal colostrum intake, reducing young animal pre-weaning mortality,reducing the number of young animals lost due to low viability, reducingthe number of weaned young animals, improving the immune status of younganimals at weaning, reducing the number of lightweight young animalsfrom nursery to market, increasing the number of young animals marketedper sow, and increasing calculated litter weight gain. The immune statusof young animals can comprise total immunoglobulins in blood.

The amount of clay in a feed composition can range from about 0.1 lb/tonto 10 lb/ton. The amount of clay in a gestation feed composition canrange from about 0.5 lb/ton to 4.0 lb/ton. Further, the amount of clayin a lactation feed composition can range from about 0.5 lb/ton to 08lb/ton.

Further, the amount of clay administered to a sow can range from about1.0 g/d to about 10 g/d, from about 0.1 g/d to about 8 g/d, from about0.5 g/d to about 3 g/d, or from about 4.0 g/d to about 7 g/d. Further,when the animal is a pig, the clay can be administered starting on day 3to 93 of gestation.

Another aspect of the disclosure encompasses a method of increasing theamount of piglet colostrum intake, reducing pre-weaning mortality,reducing the number of piglets lost due to low viability, reducing thenumber of weaned pigs, reducing the number of lightweight pigs fromnursery to market, increasing the number of pigs marketed per sow, andincreasing calculated litter weight gain. The method comprises orallyadministering to a sow a therapeutically effective amount of a clay. Insome aspects, the sow is parity 2 or parity 6 or more.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,when the animal is a pig, the clay is administered starting on day 3 today 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.5 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 0.5 lb/ton to 0.8 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, when theanimal is a pig, the clay can be administered starting on day 3 to 93 ofgestation.

Another aspect of the disclosure encompasses method of reducingembryonic loss, increasing litter size, increasing the number of livebirths, improving the immune status of the maternal animal, reducing theconcentration of maternal fecal amino acids, reducing the concentrationof maternal fecal short-chained amino acid, and increasing litter birthweight. The method comprises orally administering to a sow an effectiveamount of a therapeutic clay. In some aspects, the sow is parity 2 orparity 6 or more.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,the clay is administered starting on day 3 to day 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.5 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 0.5 lb/ton to 0.8 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, when theanimal is a pig, the clay can be administered starting on day 3 to 93 ofgestation.

Yet another aspect of the disclosure encompasses a method of enhancingpig litter performance. The method comprises orally administering aneffective amount of a therapeutic day to a sow. In some aspects, the sowis parity 2, or parity 6 or more.

Enhancing litter performance can comprise increasing the amount ofpiglet colostrum intake, reducing pre-weaning mortality, reducing thenumber of piglets lost due to low viability, reducing the number ofweaned pigs, improving the immune status of piglets at weaning, reducingthe number of lightweight piglets from nursery to market, increasing thenumber of pigs marketed per sow, and increasing calculated litter weightgain.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,the clay is administered starting on day 3 to day 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.5 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 0.5 lb/ton to 0.8 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, when theanimal is a pig, the clay can be administered starting on day 3 to 93 ofgestation.

An additional aspect of the disclosure encompasses a method of enhancingreproductive performance of a sow, the method comprising administeringto the sow an effective amount of a therapeutic clay. In some aspects,the sow is parity 2, or parity 6 or more.

Improving reproductive performance can comprise reducing embryonic loss,increasing litter size, increasing the number of live births, improvingthe immune status of the maternal animal, reducing the concentration ofmaternal fecal amino acids, reducing the concentration of maternal fecalshort-chained amino acid, and increasing litter birth weight.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,the clay is administered starting on day 3 to day 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.5 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 0.5 lb/ton to 0.8 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, when theanimal is a pig, the clay can be administered starting on day 3 to 93 ofgestation.

One aspect of the present disclosure encompasses a method of improvingpig litter performance, the method comprising orally administering aneffective amount of a therapeutic clay to a sow. Improving litterperformance can comprise increasing amount of young animal colostrumintake, reducing young animal pre-weaning mortality, reducing the numberof young animals lost due to low viability, reducing the number ofweaned young animals, improving the immune status of young animals atweaning, reducing the number of lightweight young animals from nurseryto market, increasing the number of young animals marketed per sow, andincreasing calculated litter weight gain.

The clay can be formulated in a feed composition for oral administrationto the animal. The clay can be administered during gestation, duringlactation, and combinations thereof. For instance, the clay can beadministered for a period of time during gestation. In some aspects, theclay is administered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,the clay is administered starting on day 3 to day 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.5 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 0.5 lb/ton to 0.8 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, when theanimal is a pig, the clay can be administered starting on day 3 to 93 ofgestation.

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure is directed to methods of using therapeutic clayto improve efficiency, growth, and performance in animal production.Specifically, it was discovered that orally administering a therapeuticclay to an animal improves reproductive performance and litterperformance in a mammalian animal. Surprisingly, administering the clayto a maternal animal improves performance of the litter even afterweaning the young animals, and without administering the clay to theweaned animals. For instance, administering the clay to a maternalanimal reduces the number of lightweight young animals from nursery tomarket and increases the number of young animals marketed per sow, eventhough the animals are not administered the clay.

I. Therapeutic Clay

In one aspect, the present disclosure provides a therapeutic clay. Theclay is administered orally. In some aspects, the clay is formulatedwith other ingredients to facilitate oral administration and effectiveuse. For instance, the therapeutic clay may be formulated with nutritiveor other pharmaceutical agents for administration to an animal. The clayand formulations comprising the therapeutic clay are described below.

A. Clay

The term “clay” as used herein refers to a fine-grained natural rock orsoil material that combines one or more clay minerals with traces ofmetal oxides and organic matter. Clays from natural geologic claydeposits are mostly composed of silicate minerals containing variableamounts of water trapped in the mineral structure. Additionally, as itwill be recognized by an individual skilled in the art, clay may furthercomprise various amounts of metal oxides, organic matter, and othermaterials that can be mixed in with the clay. Sometimes clays comprisevarying amounts of iron, magnesium, alkali metals, alkaline earths andother cations. Depending on the content of the soil, clay can appear invarious colors, from white to dull gray or brown to a deep orange-red.Clays may be broadly classified into swelling clays, non-swelling days,and mixed layer clays.

Any clay may be used in a composition or method of the presentdisclosure, provided the clay has therapeutic properties. Withoutwishing to be bound by theory, therapeutic properties of the clay mayinclude antimicrobial properties, antitoxin properties, as well as otherproperties that may contribute to the therapeutic properties of the claydistinct from antimicrobial to antitoxin activity. Conversely, atherapeutic clay can provide the desired therapeutic qualities withouthaving antimicrobial properties or antitoxin properties. In someaspects, a therapeutic clay has therapeutic properties of the claydistinct from antimicrobial to antitoxin activity. A clay havingtherapeutic properties suitable for a method of the disclosure can be asdescribed in U.S. patent application Ser. No. 15/266,570, the disclosureof which is incorporated herein by reference in its entirety.

In some aspects, a therapeutic clay can be combined with other clays.For instance, the therapeutic clay can be combined with other clays at aratio of about 1:99 therapeutic clay to other clays, to about 99:1therapeutic clay to other clays; at a ratio of about 80:20 therapeuticclay to other clays, to about 30:70 therapeutic clay to other clays; orat a ratio of about 45:55 therapeutic clay to other clays. In someaspects, the therapeutic clay can be combined with a bentonite clay.

A therapeutic clay may be a swelling clay, a non-swelling clay, a mixedlayer clay, or a combination of a swelling clay, a non-swelling clay,and a mixed layer clay. In some aspects, the clay of the presentdisclosure is a swelling clay. Swelling or expansive clays are claysprone to large volume changes (swelling and shrinking) that are directlyrelated to changes in water content. Swelling clays are generallyreferred to as smectite clays. Smectite clays have approximately 1-nmthick 2:1 layers (c-direction of unit cell) separated by hydratedinterlayer cations which give rise to the clay's swelling. The “a” and“b” dimensions of the mineral are on the order of several microns. Thelayers themselves are composed of two opposing silicate sheets, whichcontain Si and Al in tetrahedral coordination with oxygen, separated byan octahedral sheet that contains Al, Fe and Mg in octahedralcoordination with hydroxyls. The surfaces of the 2:1 layers (twotetrahedral sheets with an octahedral sheet in between) carry a netnegative charge that is balanced by interlayer cations. The chargedsurfaces of the 2:1 layers attract cations and water, which leads toswelling.

Smectite clays may be classified with respect to the location of thenegative charge on the 2:1 layers, and based on the composition of theoctahedral sheet (either dioctahedral or trioctahedral). Dioctahedralsmectites include beidellite having the majority of charge in thetetrahedral sheet, and montmorillonite having the majority of charge inthe octahedral sheet. Similar trioctahedral smectites are saponite andhectorite. Swelling and other properties of smectite can be altered byexchanging the dominant interlayer cation. For example, swelling can belimited to 2 water layers by exchanging Na for Ca.

Smectite clays may be naturally mined. Alternatively, smectite clays maybe synthesized. Methods of synthesizing smectite clays may be asdescribed in U.S. Pat. No. 4,861,584, the disclosure of which isincorporated by reference herein in its entirety.

In other aspects, a therapeutic clay of the present disclosure is anon-swelling clay, also generally known as illite clays. Illite claysare similar in structure to smectite clays, but have their 2:1 layersbound together by poorly hydrated potassium ions, and for that reason donot swell.

In preferred aspects, a therapeutic clay of the present disclosure is amixed-layer clay. Mixed-layer clays are generally referred to asrectorite and are composed of ordered mixed layers of illite andsmectite. Layers of illite and smectite in rectorite clays may be randomor regular. Ordering of illite and smectite layers in rectorite may bereferred to as R⁰ ordered or R¹ ordered illite-smectite. R¹-orderedillite-smectite is ordered in an ISISIS fashion, whereas R⁰ describesrandom ordering. Other advanced ordering types may also be described. Insome aspects, a clay of the present disclosure is a rectorite having R¹ordered layers of illite and smectite.

A therapeutic clay of the present disclosure is a K-rectorite. Morepreferably, the therapeutic clay is a K-rectorite comprising therapeuticeffective amounts of a reducing agent. Even more preferred, thetherapeutic clay is a K-rectorite comprising therapeutic effectiveamounts of pyrite, or a K-rectorite comprising therapeutic effectiveamounts of Fe³⁺.

A therapeutic clay of the present disclosure may be an unrefinednaturally occurring therapeutic clay. Alternatively, the clay may be arefined clay purified from other material normally present in naturallyoccurring clay. Additionally, a clay may be purified to provide asubstantially single form of the therapeutic clay. For instance, whenthe clay is a rectorite clay, the clay may be purified to provide asubstantially pure K-rectorite clay, a substantially pure Na-rectoriteclay, or a substantially pure Ca-rectorite clay. In some aspects, theclay is a naturally occurring therapeutic clay. In other aspects, thetherapeutic clay is a refined clay. In other aspects, the therapeuticclay is a purified clay.

In some aspects, the therapeutic clay is an unrefined, naturallyoccurring therapeutic clay. In another aspect, the clay is a refinednaturally occurring therapeutic clay. In yet other aspects, the clay issynthesized. Methods of synthesizing therapeutic clays may be asdescribed in U.S. Patent Publication No. 2013/0004544, the disclosure ofwhich is incorporated by reference herein in its entirety. In otheraspects, therapeutic clays are naturally mined, and the levels ofreducing agents in the mined clays are adjusted to provide therapeuticeffective amounts of reducing agents in the clay.

In some aspects, the therapeutic clay of the present disclosure is anaturally mined clay from an open pit mine in hydrothermally altered,pyroclastic material in the Cascade Mountains. Without wishing to bebound by theory, the therapeutic properties of the clay may be due to arare transition metal combination, including a level of pyrite rangingfrom about 3% to about 10% wt/wt and/or a level of pyrite ranging fromabout 1% to about 5% wt/wt.

In other aspects, the clay of the present disclosure is a natural redclay mined in the Cascade Mountain region of Oregon, more specifically ared clay mined in the crater lake region of the Cascade Mountains ofOregon. Without wishing to be bound by theory, the therapeuticproperties of the red clay may be due to the presence of therapeuticeffective amounts of aluminum as described above, among otherproperties.

The clay may also be modified with various substituents to alter theproperties of the day. Non-limiting examples of modifications includemodification with organic material, polymers, reducing agents, andvarious elements such as sodium, iron, silver, or bromide, or bytreatment with a strong acid. In some aspects, a clay of the presentdisclosure is modified with reducing metal oxides. In some alternativesof the aspects, when the clay is modified with reducing metal oxides,the day is modified with pyrite.

The particle size of the clay may be an important factor that caninfluence its effectiveness, as well as bioavailability, blenduniformity, segregation, and flow properties. In general, smallerparticle sizes of clay increase its effectiveness by increasing thesurface area. In various aspects, the average particle size of the clayis less than about 500 microns in diameter, or less than about 450microns in diameter, or less than about 400 microns in diameter, or lessthan about 350 microns in diameter, or less than about 300 microns indiameter, or less than about 250 microns in diameter, or less than about200 microns in diameter, or less than about 150 microns in diameter, orless than about 100 microns in diameter, or less than about 75 micronsin diameter, or less than about 50 microns in diameter, or less thanabout 25 microns in diameter, or less than about 15 microns in diameter.In some applications, the use of particles less than 15 microns indiameter may be advantageous. Preferably, the average particle size ofthe clay is about 1 to about 200 microns in diameter, preferably fromabout 10 to about 150 microns in diameter.

Similarly, in aspects wherein a reducing agent may be added to a clay,the particle size of a reducing agent may also be an important factorthat can influence its effectiveness, and in general, smaller particlesizes increase its effectiveness. Preferably, the average particle sizeof the reducing agent that may be added to the clay is less than 1micron in size.

B. Dietary Supplements or Feed Compositions Comprising a TherapeuticClay

One aspect of the present invention provides dietary supplements or feedcompositions comprising a therapeutically effective amount of atherapeutic clay. An effective amount of a therapeutic clay in a feedsupplement composition can and will vary depending on the clay, the bodyweight, sex, age and/or medical condition of the animal, the severityand extent of the infectious disease in the animal, the method ofadministration, the duration of treatment, as well as the species of theanimal, and may be determined experimentally using methods known in theart.

Generally, the amount of a therapeutic clay present in a feed orsupplement composition will be at least 0.001% (w/w) of the totalcomposition. In one aspect, the amount of clay in the composition rangesfrom about 0.001% to about 100% (w/w). For instance, the amount of clayin the composition may range from about 0.001% to about 50% (w/w), fromabout 25% to about 75% (w/w), or about 50% to about 100% (w/w).Preferably, the amount of clay in a feed or supplement compositionranges from between about 0.001% to about 15% (w/w), more preferablyfrom about 0.1% to about 10% (w/w), and even more preferably from about0.1% to about 0.5% (w/w).

The terms “feed”, “food”, “feed composition”, and “feed supplement”, areused herein interchangeably and may refer to any feed compositionnormally fed to an animal. Feed compositions normally fed to an animalare known in the art. A feed composition may include one or morecomponents of an animal feed. Non-limiting examples of feed matter oranimal feed matter may include, without limitation: corn or a componentof corn, such as, for example, corn meal, corn fiber, corn hulls, cornDDGS (distiller's dried grain with solubles), silage, ground corn, corngerm, corn gluten, corn oil, or any other portion of a corn plant; soyor a component of soy, such as, for example, soy oil, soy meal, soyhulls, soy silage, ground soy, or any other portion of a soy plant,wheat or any component of wheat, such as, for example, wheat meal, wheatfiber, wheat hulls, wheat chaff, ground wheat, wheat germ, or any otherportion of a wheat plant; canola, such as, for example, canola oil,canola meal, canola protein, canola hulls, ground canola, or any otherportion of a canola plant; sunflower or a component of a sunflowerplant; sorghum or a component of a sorghum plant; sugar beet or acomponent of a sugar beet plant; cane sugar or a component of asugarcane plant; barley or a component of a barley plant; palm oil, palmkernel or a component of a palm plant; glycerol; corn steep liquor: awaste stream from an agricultural processing facility; lecithin; rumenprotected fats: molasses; soy molasses: flax: peanuts; peas; oats;grasses, such as orchard grass and fescue; fish meal, meat & bone meal;feather meal: and poultry byproduct meal; and alfalfa and/or clover usedfor silage or hay, and various combinations of any of the feedingredients set forth herein, or other feed ingredients generally knownin the art. As it will be recognized in the art, a feed composition mayfurther be supplemented with amino acids, vitamins, minerals, and otherfeed additives such as other types of enzymes, organic acids, essentialoils, probiotics, prebiotics, antioxidants, pigments, anti-cakingagents, and the like, as described further below.

A feed composition may be formulated for administration to any animalsubject. Suitable subjects include all mammals, avian species, andaquaculture. Non-limiting examples of food animals include poultry(e.g., chickens, including broilers, layers, and breeders, ducks, gamehens, geese, guinea fowl/hens, quail, and turkeys), beef cattle, dairycattle, veal, pigs, goats, sheep, bison, and fishes. Suitable companionanimals include, but are not limited to, cats, dogs, horses, rabbits,rodents (e.g., mice, rats, hamsters, gerbils, and guinea pigs),hedgehogs, and ferrets. Examples of research animals include rodents,cats, dogs, rabbits, pigs, and non-human primates. Non-limiting examplesof suitable zoo animals include non-human primates, lions, tigers,bears, elephants, giraffes, and the like.

According to various aspects of the present invention, the feed may bein any suitable form known in the animal feed art, and may be a wet ordry component. For example, according to certain aspects, the feedcomposition may be in a form selected from the group consisting of acomplete feed, a feed supplement, a feed additive, a premix, atop-dress, a tub, a mineral, a meal, a block, a pellet, a mash, a liquidsupplement, a drench, a bolus, a treat, and combinations of any thereof.Additionally, a feed sample may optionally be ground before preparing afeed composition.

The dietary supplements or feed compositions may optionally comprise atleast one additional nutritive and/or pharmaceutical agent. Forinstance, the at least one additional nutritive and/or pharmaceuticalagent may be selected from the group consisting of vitamin, mineral,amino acid, antioxidant, probiotic, essential fatty acid, andpharmaceutically acceptable excipient. The compositions may include oneadditional nutritive and/or pharmaceutical component or a combination ofany of the foregoing additional components in varying amounts. Suitableexamples of each additional component are detailed below.

a. Vitamins

Optionally, the dietary supplement of the invention may include one ormore vitamins. Suitable vitamins for use in the dietary supplementinclude vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K,riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine,thiamine, pantothenic acid, and biotin. The form of the vitamin mayinclude salts of the vitamin, derivatives of the vitamin, compoundshaving the same or similar activity of a vitamin, and metabolites of avitamin.

The dietary supplement may include one or more forms of an effectiveamount of any of the vitamins described herein or otherwise known in theart. Non-limiting examples of vitamins include vitamin K, vitamin D,vitamin C, and biotin. An “effective amount” of a vitamin typicallyquantifies an amount at least about 10% of the United States RecommendedDaily Allowance (“RDA”) of that particular vitamin for a subject. It iscontemplated, however, that amounts of certain vitamins exceeding theRDA may be beneficial for certain subjects. For example, the amount of agiven vitamin may exceed the applicable RDA by 100%, 200%, 300%, 400%,500% or more.

b. Minerals

In addition to the metal chelates or metal salts described in SectionIA, the dietary supplement may include one or more minerals or mineralsources. Non-limiting examples of minerals include, without limitation,calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese,molybdenum, phosphorus, potassium, and selenium. Suitable forms of anyof the foregoing minerals include soluble mineral salts, slightlysoluble mineral salts, insoluble mineral salts, chelated minerals,mineral complexes, non-reactive minerals such as carbonyl minerals, andreduced minerals, and combinations thereof.

In an aspect, the mineral may be a form of calcium. Suitable forms ofcalcium include calcium alpha-ketoglutarate, calcium acetate, calciumalginate, calcium ascorbate, calcium aspartate, calcium caprylate,calcium carbonate, calcium chelates, calcium chloride, calcium citrate,calcium citrate malate, calcium formate, calcium glubionate, calciumglucoheptonate, calcium gluconate, calcium glutarate, calciumglycerophosphate, calcium lactate, calcium lysinate, calcium malate,calcium orotate, calcium oxalate, calcium oxide, calcium pantothenate,calcium phosphate, calcium pyrophosphate, calcium succinate, calciumsulfate, calcium undecylenate, coral calcium, dicalcium citrate,dicalcium malate, dihydroxycalcium malate, dicalcium phosphate, andtricalcium phosphate.

Generally speaking, the dietary supplement may include one or more formsof an effective amount of any of the minerals described herein orotherwise known in the art. An “effective amount” of a mineral typicallyquantifies an amount at least about 10% of the United States RecommendedDaily Allowance (“RDA”) of that particular mineral for a subject. It iscontemplated, however, that amounts of certain minerals exceeding theRDA may be beneficial for certain subjects. For example, the amount of agiven mineral may exceed the applicable RDA by 100%, 200%, 300%, 400%,500% or more. Typically, the amount of mineral included in the dietarysupplement may range from about 1 mg to about 1500 mg, about 5 mg toabout 500 mg, or from about 50 mg to about 500 mg per dosage.

c. Essential Fatty Acids

Optionally, the dietary supplement may include a source of an essentialfatty acid. The essential fatty acid may be isolated or it may be an oilsource or fat source that contains an essential fatty acid. In oneaspect, the essential fatty acid may be a polyunsaturated fatty acid(PUFA), which has at least two carbon-carbon double bonds generally inthe cis-configuration. The PUFA may be a long chain fatty acid having atleast 18 carbons atoms. The PUFA may be an omega-3 fatty acid in whichthe first double bond occurs in the third carbon-carbon bond from themethyl end of the carbon chain (i.e., opposite the carboxyl acid group).Examples of omega-3 fatty acids include alpha-linolenic acid (18:3,ALA), stearidonic acid (18:4), eicosatetraenoic acid (20:4),eicosapentaenoic acid (20:5; EPA), docosatetraenoic acid (22:4), n-3docosapentaenoic acid (22:5; n-3DPA), and docosahexaenoic acid (22:6;DHA). The PUFA may also be an omega-5 fatty acid, in which the firstdouble bond occurs in the fifth carbon-carbon bond from the methyl end.Non-limiting examples of omega-5 fatty acids include myristoleic acid(14:1), myristoleic acid esters, and cetyl myristoleate. The PUFA mayalso be an omega-6 fatty acid, in which the first double bond occurs inthe sixth carbon-carbon bond from the methyl end. Examples of omega-6fatty acids include linoleic acid (18:2), gamma-linolenic acid (18:3),eicosadienoic acid (20:2), dihomo-gamma-linolenic acid (20:3),arachidonic acid (20:4), docosadienoic acid (22:2), adrenic acid (22:4),and n-6 docosapentaenoic acid (22:5). The fatty acid may also be anomega-9 fatty acid, such as oleic acid (18:1), eicosenoic acid (20:1),mead acid (20:3), erucic acid (22-1), and nervonic acid (24:1).

In another aspect, the essential fatty acid source may be aseafood-derived oil. The seafood may be a vertebrate fish or a marineorganism, such that the oil may be fish oil or marine oil. The longchain (20C, 22C) omega-3 and omega-6 fatty acids are found in seafood.The ratio of omega-3 to omega-6 fatty acids in seafood ranges from about8:1 to 20:1. Seafood from which oil rich in omega-3 fatty acids may bederived includes, but is not limited to, abalone scallops, albacoretuna, anchovies, catfish, clams, cod, gem fish, herring, lake trout,mackerel, menhaden, orange roughy, salmon, sardines, sea mullet, seaperch, shark, shrimp, squid, trout, and tuna.

In yet another aspect, the essential fatty acid source may be aplant-derived oil. Plant and vegetable oils are rich in omega-6 fattyacids. Some plant-derived oils, such as flaxseed oil, are especiallyrich in omega-3 fatty acids. Plant or vegetable oils are generallyextracted from the seeds of a plant, but may also be extracted fromother parts of the plant. Plant or vegetable oils that are commonly usedfor cooking or flavoring include, but are not limited to, acai oil,almond oil, amaranth oil, apricot seed oil, argan oil, avocado seed oil,babassu oil, ben oil, blackcurrant seed oil, Borneo tallow nut oil,borage seed oil, buffalo gourd oil, canola oil, carob pod oil, cashewoil, castor oil, coconut oil, coriander seed oil, corn oil, cottonseedoil, evening primrose oil, false flax oil, flax seed oil, grapeseed oil,hazelnut oil, hemp seed oil, kapok seed oil, lallemantia oil, linseedoil, macadamia oil, meadowfoam seed oil, mustard seed oil, okra seedoil, olive oil, palm oil, palm kernel oil, peanut oil, pecan oil, pequioil, perilla seed oil, pine nut oil, pistachio oil, poppy seed oil,prune kernel oil, pumpkin seed oil. quinoa oil, ramtil oil, rice branoil, safflower oil, sesame oil, soybean oil, sunflower oil, tea oil,thistle oil, walnut oil, or wheat germ oil. The plant-derived oil mayalso be hydrogenated or partially hydrogenated.

In still a further aspect, the essential fatty acid source may be analgae-derived oil. Commercially available algae-derived oils includethose from Crypthecodinium cohnii and Schizochytrium sp. Other suitablespecies of algae, from which oil is extracted, include Aphanizomenonflos-aquae, Bacilliarophy sp., Botryococcus braunii, Chlorophyceae sp.,Dunaliella tertiolecta, Euglena gracilis, Isochrysis galbana,Nannochloropsis salina, Nannochloris sp., Neochloris oleoabundans,Phaeodactylum tricornutum, Pleurochrysis carterae, Prymnesium parvum,Scenedesmus dimorphus, Spirulina sp., and Tetraselmis chui.

d. Amino Acids

The dietary supplement may optionally include from one to several aminoacids. Suitable amino acids include alanine, arginine, asparagine,aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine,isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine,threonine, tryptophan, tyrosine, and valine or their hydroxy analogs. Incertain aspects, the amino acid will be selected from the essentialamino acids. An essential amino acid is generally described as one thatcannot be synthesized de novo by the organism, and therefore, must beprovided in the diet. By way of non-limiting example, the essentialamino acids for humans include: L-histidine, L-isoleucine, L-leucine,L-lysine. L-methionine, L-phenylalanine, L-valine and L-threonine.

e. Antioxidants

The dietary supplement may include one or more suitable antioxidants. Aswill be appreciated by a skilled artisan, the suitability of a givenantioxidant will vary depending upon the species to which the dietarysupplement will be administered. Non-limiting examples of antioxidantsinclude ascorbic acid and its salts, ascorbyl palmitate, ascorbylstearate, anoxomer, N-acetylcysteine, benzyl isothiocyanate, o-, m- orp-amino benzoic acid (o is anthranilic acid, p is PABA), butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), caffeic acid,canthaxantin, alpha-carotene, beta-carotene, beta-caraotene,beta-apo-carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate,chlorogenic acid, citric acid and its salts, p-coumaric acid, curcurin,3,4-dihydroxybenzoic acid, N,N′-diphenyl-p-phenylenediamine (DPPD),dilauryl thiodipropionate, distearyl thiodipropionate,2,6-di-tert-butylphenol, dodecyl gallate, edetic acid, ellagic acid,erythorbic acid, sodium erythorbate, esculetin, esculin,6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, ethyl gallate, ethylmaltol, ethylenediaminetetraacetic acid (EDTA), eugenol, ferulic acid,flavonoids, flavones (e.g., apigenin, chrysin, luteolin), flavonols(e.g., datiscetin, myricetin, daemfero), flavanones, fraxetin, fumaricacid, gallic acid, gentian extract, gluconic acid, glycine, gumguaiacum, hesperetin, alpha-hydroxybenzyl phosphinic acid,hydroxycinammic acid, hydroxyglutaric acid, hydroquinone,N-hydroxysuccinic acid, hydroxytryrosol, hydroxyurea, lactic acid andits salts, lecithin, lecithin citrate; R-alpha-lipoic acid, lutein,lycopene, malic acid, maltol, 5-methoxy tryptamine, methyl gallate,monoglyceride citrate, monoisopropyl citrate; morin,beta-naphthoflavone, nordihydroguaiaretic acid (NDGA), octyl gallate,oxalic acid, palmityl citrate, phenothiazine, phosphatidylcholine,phosphoric acid, phosphates, phytic acid, phytylubichromel, propylgallate, polyphosphates, quercetin, trans-resveratrol, rosmarinic acid,sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate,syringic acid, tartaric acid, thymol, tocopherols (i.e. alpha-, beta-,gamma- and delta-tocopherol), tocotrienols (i.e., alpha-, beta-, gamma-and delta-tocotrienols), tyrosol, vanilic acid,2,6-di-tert-butyl-4-hydroxymethylphenol (i.e., lonox 100),2,4-(tris-3′,5′-bi-tert-butyl-4′-hydroxybenzyl)-mesitylene (i.e., lonox330), 2,4,5-trihydroxybutyrophenone, ubiquinone, tertiary butylhydroquinone (TBHQ), thiodipropionic acid, trihydroxy butyrophenone,tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10,zeaxanthin, or combinations thereof.

Natural antioxidants that may be included in the dietary supplementinclude, but are not limited to, apple peel extract, blueberry extract,carrot juice powder, clove extract, coffeeberry, coffee bean extract,cranberry extract, eucalyptus extract, ginger powder, grape seedextract, green tea, olive leaf, parsley extract, peppermint, pimentoextract, pomace, pomegranate extract, ice bran extract, rosehips,rosemary extract, sage extract, tart cherry extract, tomato extract,turmeric, and wheat germ oil.

f. Anti-Inflammatory Agents

The dietary supplement may optionally include at least oneanti-inflammatory agent. In one aspect, the anti-inflammatory agent maybe a synthetic non-steroidal anti-inflammatory drug (NSAID) such asacetylsalicylic acid, dichiophenac, indomethacin, oxamethacin,ibuprofen, indoprofen, naproxen, ketoprofen, mefamanic acid, metamizole,piroxicam, and celecoxib. In an alternate aspect, the anti-inflammatoryagent may be a prohormone that modulates inflammatory processes.Suitable prohormones having this property include prohormone convertase1, proopiomelanocortin, prohormone B-type natriuretic peptide, SMR1prohormone, and the like. In another aspect, the anti-inflammatory agentmay be an enzyme having anti-inflammatory effects. Examples ofanti-inflammatory enzymes include bromelain, papain, serrapeptidase, andproteolytic enzymes such as pancreatin (a mixture of trypsin, amylaseand lipase).

In still another aspect, the anti-inflammatory agent may be a peptidewith anti-inflammatory effects. For example, the peptide may be aninhibitor of phospholipase A2, such as antiflammin-1, a peptide thatcorresponds to amino acid residues 246-254 of lipocortin; antiflammin-2,a peptide that corresponds to amino acid residues 39-47 of uteroglobin;S7 peptide, which inhibits the interaction between interleukin 6 andinterleukin 6 receptor; RP1, a prenyl protein inhibitor; and similarpeptides. Alternatively, the anti-inflammatory peptide may becortistatin, a cyclic neuropeptide related to somatostatin, or peptidesthat correspond to an N-terminal fragment of SV-IV protein, a conservedregion of E-, L-, and P-selectins, and the like. Other suitableanti-inflammatory preparations include collagen hydrolysates and milkmicronutrient concentrates (e.g., MicroLactin® available from StolleMilk Biologics, Inc., Cincinnati, OH), as well as milk proteinhydrolysates, casein hydrolysates, whey protein hydrolysates, and plantprotein hydrolysates.

In a further aspect, the anti-inflammatory agent may be a probiotic thathas been shown to modulate inflammation. Suitable immunomodulatoryprobiotics include lactic acid bacteria such as acidophilli,lactobacilli, and bifidophilli. In yet another aspect, theanti-inflammatory agent may be a plant extract having anti-inflammatoryproperties. Non-limiting examples of suitable plant extracts withanti-inflammatory benefits include blueberries, boswella, black catechuand Chinese skullcap, celery seed, chamomile, cherries, devils claw,eucalyptus, evening primrose, ginger, hawthorne berries, horsetail,Kalopanax pictus bark, licorice root, turmeric, white wallow, willowbark, and yucca.

g. Probiotics

Probiotics and prebiotics may include yeast and bacteria that helpestablish an immune protective rumen or gut microflora as well as smalloligosaccharides. By way of non-limiting example, yeast-derivedprobiotics and prebiotics include yeast cell wall derived componentssuch as β-glucans, arabinoxylan isomaltose, agarooligosaccharides,lactosucrose, cyclodextrins, lactose, fructooligosaccharides,laminariheptaose, lactulose, β-galactooligosaccharides,mannanoligosaccharides, raffinose, stachyose, oligofructose, glucosylsucrose, sucrose thermal oligosaccharide, isomalturose, caramel, inulin,and xylooligosaccharides. In one aspect, the yeast-derived agent may beβ-glucans and/or mannanoligosaccharides. Sources for yeast cell wallderived components include Saccharomyces bisporus, Saccharomycesboulardii, Saccharomyces cerevisiae, Saccharomyces capsularis.Saccharomyces delbrueckii, Saccharomyces fermentati, Saccharomyceslugwigii, Saccharomyces microellipsoides, Saccharomyces pastorianus.Saccharomyces rosei, Candida albicans, Candida cloaceae, Candidatropicalis, Candida utilis, Geotrichum candidum, Hansenula americana,Hansenula anomala, Hansenula wingei, and Aspergillus oryzae.

Probiotics and prebiotics may also include bacteria cell wall derivedagents such as peptidoglycan and other components derived fromgram-positive bacteria with a high content of peptidoglycan. Exemplarygram-positive bacteria include Lactobacillus acidophilus, Bifedobactthermophilum, Bifedobat longhum, Streptococcus faecium, Bacilluspumilus, Bacillus subtilis. Bacillus licheniformis, Lactobacillusacidophilus, Lactobacillus casei, Enterococcus faecium, Bifidobacteriumbifidium, Propionibacterium acidipropionici, Propionibacteriiumfreudenreichii, and Bifidobacterium pseudolongum.

h. Herbals

Suitable herbals and herbal derivatives, as used herein, refer to herbalextracts, and substances derived from plants and plant parts, such asleaves, flowers and roots, without limitation. Non-limiting exemplaryherbals and herbal derivatives include agrimony, alfalfa, aloe vera,amaranth, angelica, anise, barberry, basil, bayberry, bee pollen, birch,bistort, blackberry, black cohosh, black walnut, blessed thistle, bluecohosh, blue vervain, boneset, borage, buchu, buckthorn, bugleweed,burdock, phytogenic, cayenne, caraway, cascara sagrada, catnip, celery,centaury, chamomile, chaparral, chickweed, chicory, chinchona, cloves,coltsfoot, comfrey, cornsilk, couch grass, cramp bark, culver's root,cyani, cornflower, damiana, dandelion, devils claw, dong quai,echinacea, elecampane, ephedra, eucalyptus, evening primrose, eyebright,false unicorn, fennel, fenugreek, figwort, flaxseed, garlic, gentian,ginger, ginseng, golden seal, gotu kola, gum weed, hawthorn, hops,horehound, horseradish, horsetail, hoshouwu, hydrangea, hyssop, icelandmoss, irish moss, jojoba, juniper, kelp, lady's slipper, lemon grass,licorice, lobelia, mandrake, marigold, marjoram, marshmallow, mistletoe,mullein, mustard, myrrh, nettle, oatstraw, oregon grape, papaya,parsley, passion flower, peach, pennyroyal, peppermint, periwinkle,plantain, pleurisy root, pokeweed, prickly ash, psyllium, quassia, queenof the meadow, red clover, red raspberry, redmond clay, rhubarb, rosehips, rosemary, rue, safflower, saffron, sage, St. John's wort,sarsaparilla, sassafras, saw palmetto, skullcap, senega, senna,shepherd's purse, slippery elm, spearmint, spikenard, squawvine,stillingia, strawberry, taheebo, thyme, Uva ursi, valerian, violet,watercress, white oak bark, white pine bark, wild cherry, wild lettuce,wild yam, willow, wintergreen, witch hazel, wood betony, wormwood,yarrow, yellow dock, yerba santa, yucca and combinations thereof.

i. Pigments

Suitable non-limiting pigments include actinioerythrin, alizarin,alloxanthin, β-apo-2′-carotenal, apo-2-lycopenal, apo-6′-lycopenal,astacein, astaxanthin, azafrinaldehyde, aacterioruberin, aixin,α-carotine, β-carotine, γ-carotine, β-carotenone, canthaxanthin,capsanthin, capsorubin, citranaxanthin, citroxanthin, crocetin,crocetinsemialdehyde, crocin, crustaxanthin, cryptocapsin,α-cryptoxanthin, β-cryptoxanthin, cryptomonaxanthin, cynthiaxanthin,decaprenoxanthin, dehydroadonirubin, diadinoxanthin,1,4-diamino-2,3-dihydroanthraquinone, 1,4-dihydroxyanthraquinone,2,2′-Diketospirilloxanthin, eschscholtzxanthin, eschscholtzxanthone,flexixanthin, foliachrome, fucoxanthin, gazaniaxanthin,hexahydrolycopene, hopkinsiaxanthin, hydroxyspheriodenone,isofucoxanthin, loroxanthin, lutein, luteoxanthin, lycopene,lycopersene, lycoxanthin, morindone, mutatoxanthin, neochrome,neoxanthin, nonaprenoxanthin, OH-Chlorobactene, okenone, oscillaxanthin,paracentrone, pectenolone, pectenoxanthin, peridinin, phleixanthophyll,phoeniconone, phoenicopterone, phoenicoxanthin, physalien, phytofluene,pyrrhoxanthininol, quinones, rhodopin, rhodopinal, rhodopinol,rhodovibrin, rhodoxanthin, rubixanthone, saproxanthin,semi-α-carotenone, semi-β-carotenone, sintaxanthin, siphonaxanthin,siphonein, spheroidene, tangeraxanthin, torularhodin, torularhodinmethyl ester, torularhodinaldehyde, torulene,1,2,4-trihydroxyanthraquinone, triphasiaxanthin, trollichrome,vaucheriaxanthin, violaxanthin, wamingone, xanthin, zeaxanthin,α-zeacarotene and combinations thereof.

j. Pharmaceutical Agents

Suitable non-limiting pharmaceutically acceptable agents include anacid/alkaline-labile drug, a pH dependent drug, or a drug that is a weakacid or a weak base. Examples of acid-labile drugs include statins(e.g., pravastatin, fluvastatin and atorvastatin), antibiotics (e.g.,penicillin G, ampicillin, streptomycin, erythromycin, clanthromycin andazithromycin), nucleoside analogs (e.g., dideoxyinosine (ddI ordidanosine), dideoxyadenosine (ddA), dideoxycytosine (ddC)), salicylates(e.g., aspirin), digoxin, bupropion, pancreatin, midazolam, andmethadone. Drugs that are only soluble at acid pH include nifedipine,emonapride, nicardipine, amosulalol, noscapine, propafenone, quinine,dipyridamole, josamycin, dilevalol, labetalol, enisoprost, andmetronidazole. Drugs that are weak acids include phenobarbital,phenytoin, zidovudine (AZT), salicylates (e.g., aspirin), propionic acidcompounds (e.g., ibuprofen), indole derivatives (e.g., indomethacin),fenamate compounds (e.g., meclofenamic acid), pyrrolealkanoic acidcompounds (e.g., tolmetin), cephalosporns (e.g., cephalothin,cephalaxin, cefazolin, cephradine, cephapirin, cefamandole, andcefoxitin), 6-fluoroquinolones and prostaglandins. Drugs that are weakbases include adrenergic agents (e.g., ephedrine, desoxyephedrine,phenylephrine, epinephrine, salbutamol, and terbutaline), cholinergicagents (e.g., physostigmine and neostigmine), antispasmodic agents(e.g., atropine, methantheline, and papaverine), curariform agents(e.g., chlorisondamine), tranquilizers and muscle relaxants (e.g.,fluphenazine, thioridazine, trifluoperazine, chlorpromazine, andtriflupromazine), antidepressants (e.g., amitriptyline andnortriptyline), antihistamines (e.g., diphenhydramine, chlorpheniramine,dimenhydrinate, tripelennamine, perphenazine, chlorprophenazine, andchlorprophenpyridamine), cardioactive agents (e.g., verapamil,diltiazem, gallapomil, cinnarizine, propranolol, metoprolol andnadolol), antimalarials (e.g., chloroquine), analgesics (e.g.,propoxyphene and meperidine), antifungal agents (e.g., ketoconazole anditraconazole), antimicrobial agents (e.g., cefpodoxime, proxetil, andenoxacin), caffeine, theophylline, and morphine. In another aspect, thedrug may be a biphosphonate or another drug used to treat osteoporosis.Non-limiting examples of a biphosphonate include alendronate,ibandronate, risedronate, zoledronate, pamidronate, neridronate,olpadronate, etidronate, clodronate, and tiludronate. Other suitabledrugs include estrogen, selective estrogen receptor modulators (SERMs),and parathyroid hormone (PTH) drugs. In yet another aspect, the drug maybe an antibacterial agent (antibiotic). Suitable antibiotics includeaminoglycosides (e.g., amikacin, gentamicin, kanamycin, neomycin,netilmicin, streptomycin, and tobramycin), carbecephems (e.g.:loracarbef), a carbapenem (e.g., certapenem, imipenem, and meropenem),cephalosporins (e.g., cefadroxil cefazolin, cephalexin, cefaclor,cefamandole, cephalexin, cefoxitin, cefprozil, cefuroxime, cefixime,cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime,ceftazidime, ceftibuten, ceftizoxime, and ceftriaxone), macrolides(e.g., azithromycin, clarithromycin, dirithromycin, erythromycin, andtroleandomycin), monobactam, penicillins (e.g., amoxicillin, ampicillin,carbenicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin,penicillin G, penicillin V, piperacillin, and ticarcillin), polypeptides(e.g., bacitracin, colistin, and polymyxin B), quinolones (e.g.,ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin,moxifloxacin, norfloxacin, ofloxacin, and trovafloxacin), sulfonamides(e.g., mafenide, sulfacetamide, sulfamethizole, sulfasalazine,sulfisoxazole, and trimethoprim-sulfamethoxazole), and tetracyclines(e.g., demeclocycline, doxycycline, minocycline, and oxytetracycline).In an alternate aspect, the drug may be an antiviral protease inhibitor(e.g., amprenavir, fosamprenavir, indinavir, lopinavir/ritonavir,ritonavir, saquinavir, and nelfinavir). In still another aspect, thedrug may be a cardiovascular drug. Examples of suitable cardiovascularagents include cardiotonic agents (e.g., digitalis (digoxin),ubidecarenone, and dopamine), vasodilating agents (e.g., nitroglycerin,captopril, dihydralazine, diltiazem, and isosorbide dinitrate),antihypertensive agents (e.g., alpha-methyldopa, chlortalidone,reserpine, syrosingopine, rescinnamine, prazosin, phentolamine,felodipine, propanolol, pindolol, labetalol, clonidine, captopril,enalapril, and lisonopril), beta blockers (e.g., levobunolol, pindolol,timolol maleate, bisoprolol, carvedilol, and butoxamine), alpha blockers(e.g., doxazosin, prazosin, phenoxybenzamine, phentolamine, tamsulosin,alfuzosin, and terazosin), calcium channel blockers (e.g., amlodipine,felodipine, nicardipine, nifedipine, nimodipine, nisoldipine,nitrendipine, lacidipine, lercanidipine, verapamil, gallopamil, anddiltiazem), and anticlot agents (e.g., dipyrimadole).

k. Excipients

A variety of commonly used excipients in dietary supplement formulationsmay be selected on the basis of compatibility with the activeingredients. Non-limiting examples of suitable excipients include anagent selected from the group consisting of non-effervescentdisintegrants, a coloring agent, a flavor-modifying agent, an oraldispersing agent, a stabilizer, a preservative, a diluent, a compactionagent, a lubricant, a filler, a binder, taste-masking agents, aneffervescent disintegration agent, and combinations of any of theseagents.

In one aspect, the excipient is a binder. Suitable binders includestarches, pregelatinized starches, gelatin, polyvinylpyrolidone,cellulose, methylcellulose, sodium carboxymethylcellulose,ethylcellulose, polyacrylamides, polyvinyloxoazolidone,polyvinylalcohols, C₁₂-C₁₈ fatty acid alcohol, polyethylene glycol,polyols, saccharides, oligosaccharides, polypeptides, oligopeptides, andcombinations thereof. The polypeptide may be any arrangement of aminoacids ranging from about 100 to about 300,000 daltons.

In another aspect, the excipient may be a filler. Suitable fillersinclude carbohydrates, inorganic compounds, and polyvinylpirrolydone. Byway of non-limiting example, the filler may be calcium sulfate, both di-and tri-basic, starch, calcium carbonate, magnesium carbonate,microcrystalline cellulose, dibasic calcium phosphate, magnesiumcarbonate, magnesium oxide, calcium silicate, talc, modified starches,lactose, sucrose, mannitol, and sorbitol.

The excipient may comprise a non-effervescent disintegrant. Suitableexamples of non-effervescent disintegrants include starches such as cornstarch, potato starch, pregelatinized and modified starches thereof,sweeteners, clays, such as bentonite, micro-crystalline cellulose,alginates, sodium starch glycolate, gums such as agar, guar, locustbean, karaya, pecitin, and tragacanth.

In another aspect, the excipient may be an effervescent disintegrant. Byway of non-limiting example, suitable effervescent disintegrants includesodium bicarbonate in combination with citric acid and sodiumbicarbonate in combination with tartaric acid.

The excipient may comprise a preservative. Suitable examples ofpreservatives include antioxidants, such as a-tocopherol or ascorbate,and antimicrobials, such as parabens, chlorobutanol or phenol.

In another aspect, the excipient may include a diluent. Diluentssuitable for use include pharmaceutically acceptable saccharide such assucrose, dextrose, lactose, microcrystalline cellulose, fructose,xylitol, and sorbitol; polyhydric alcohols; a starch; pre-manufactureddirect compression diluents; and mixtures of any of the foregoing.

The excipient may include flavors. Flavors incorporated into the outerlayer may be chosen from synthetic flavor oils and flavoring aromaticsand/or natural oils, extracts from plants, leaves, flowers, fruits, andcombinations thereof. By way of example, these may include cinnamonoils, oil of wintergreen, peppermint oils, clover oil, hay oil, aniseoil, eucalyptus, vanilla, citrus oil, such as lemon oil, orange oil,grape and grapefruit oil, fruit essences including apple, peach, pear,strawberry, raspberry, cherry, plum, pineapple, and apricot.

In another aspect, the excipient may include a sweetener. By way ofnon-limiting example, the sweetener may be selected from glucose (cornsyrup), dextrose, invert sugar, fructose, and mixtures thereof (when notused as a carrier); saccharin and its various salts such as the sodiumsalt; dipeptide sweeteners such as aspartame:dihydrochalcone compounds,glycyrrhizin; Stevia rebaudiana (Stevioside); chloro derivatives ofsucrose such as sucralose; sugar alcohols such as sorbitol, mannitol,sylitol, and the like.

In another aspect, the excipient may be a lubricant. Suitablenon-limiting examples of lubricants include magnesium stearate, calciumstearate, zinc stearate, hydrogenated vegetable oils, sterotex,polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate,sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

The excipient may be a dispersion enhancer. Suitable dispersants mayinclude starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin,bentonite, purified wood cellulose, sodium starch glycolate,isoamorphous silicate, and microcrystalline cellulose as high HLBemulsifier surfactants.

Depending upon the aspect, it may be desirable to provide a coloringagent in the outer layer. Suitable color additives include food, drugand cosmetic colors (FD&C), drug and cosmetic colors (D&C), or externaldrug and cosmetic colors (Ext D&C). These colors or dyes, along withtheir corresponding lakes, and certain natural and derived colorants,may be suitable for use in the present invention depending on theaspect.

The excipient may include a taste-masking agent. Taste-masking materialsinclude, e.g., cellulose hydroxypropyl ethers (HPC) such as Klucel®,Nisswo HPC and PrimaFlo HP22; low-substituted hydroxypropyl ethers(L-HPC); cellulose hydroxypropyl methyl ethers (HPMC) such asSeppifilm-LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, MP3295A,Benecel MP824, and Benecel MP843; methylcellulose polymers such asMethocel® and Metolose®; Ethylcelluloses (EC) and mixtures thereof suchas E461, Ethocel®, Aqualon&-EC, Surelease; Polyvinyl alcohol (PVA) suchas Opadry AMB; hydroxyethylcelluloses such as Natrosol®;carboxymethylcelluloses and salts of carboxymethylcelluloses (CMC) suchas Aualon®-CMC; polyvinyl alcohol and polyethylene glycol co-polymerssuch as Kollicoat IR®; monoglycerides (Myverol), triglycerides (KLX),polyethylene glycols, modified food starch, acrylic polymers andmixtures of acrylic polymers with cellulose ethers such as Eudragit®EPO, Eudragit® RD100, and Eudragit® E100; cellulose acetate phthalate;sepifilms such as mixtures of HPMC and stearic acid, cyclodextrins, andmixtures of these materials. In other aspects, additional taste-maskingmaterials contemplated are those described in U.S. Pat. Nos. 4,851,226,5,075,114, and 5,876,759, each of which is hereby incorporated byreference in its entirety.

In various aspects, the excipient may include a pH modifier. In certainaspects, the pH modifier may include sodium carbonate or sodiumbicarbonate.

The dietary supplement or feed compositions detailed herein may bemanufactured in one or several dosage forms. In one aspect, the dosageform will be an oral dosage form. Suitable oral dosage forms may includea tablet, for example a suspension tablet, a chewable tablet, aneffervescent tablet or caplet; a pill; a powder, such as a sterilepackaged powder, a dispensable powder, and an effervescent powder, acapsule including both soft or hard gelatin capsules or non-animalderived polymers, such as hydroxypropyl methylcellulose capsules (i.e.,HPMC) or pullulan; a lozenge; a sachet; a sprinkle, a reconstitutablepowder or shake; a troche; pellets; granules; liquids; lick blocks,suspensions; emulsions; or semisolids and gels. Alternatively, thedietary supplement may be incorporated into a food product or powder formixing with a liquid, or administered orally after only mixing with anon-foodstuff liquid. As will be appreciated by a skilled artisan, thedietary supplements, in addition to being suitable for administration inmultiple dosage forms, may also be administered with various dosageregimens. Additionally, the therapeutic clay may simply be added to anydosage form of a dietary supplement or feed composition.

The amount and types of ingredients (i.e., metal chelate,chondroprotective agents, vitamin, mineral, amino acid, antioxidant,yeast culture, and essential fatty acid), and other excipients useful ineach of these dosage forms, are described throughout the specificationand examples. It should be recognized that where a combination ofingredients and/or excipient, including specific amounts of thesecomponents, is described with one dosage form that the same combinationcould be used for any other suitable dosage form. Moreover, it should beunderstood that one of skill in the art would, with the teachings foundwithin this application, be able to make any of the dosage forms listedabove by combining the amounts and types of ingredients administered asa combination in a single dosage form or separate dosage forms andadministered together as described in the different sections of thespecification.

The dietary supplements of the present invention can be manufactured byconventional pharmacological techniques. Conventional pharmacologicaltechniques include, e.g., one or a combination of methods: (1) drymixing; (2) direct compression; (3) milling; (4) dry or non-aqueousgranulation; (5) wet granulation: or (6) fusion. See, e.g., Lachman etal., The Theory and Practice of Industrial Pharmacy (1986). Othermethods include, e.g., prilling, spray drying, pan coating, meltgranulation, granulation, wurster coating, tangential coating, topspraying, extruding, coacervation and the like.

II. Methods of Using

Another aspect of the present disclosure provides methods of orallyadministering to the animal an effective amount of a therapeutic clay.An effective amount of the therapeutic clay is any amount of the claythat, when administered to an animal, will improve the performance ofthe animal when compared to the performance of an animal fed a controldiet without the clay. The clay or any combination of the day with otheringredients can be used for oral administration.

Any method of oral administration can be used, provided the method is acontrolled method of administration capable of administering an accurateamount of clay to the animal. For instance, the clay can be administeredby sprinkling an accurate amount of clay over a feed composition(topping off) or by adding to drinking water to administer the accurateamount of clay upon ingestion of the feed or water by the animal.Alternatively, the clay can be formulated with a feed composition toadminister the accurate amount of clay upon ingestion of the feedcomposition by the animal.

An animal can include, without limitation, companion animals such ascats, dogs, rabbits, horses, and rodents such as gerbils: agriculturalanimals such as cows, dairy cows, dairy calves, beef cattle, pigs,goats, sheep, horses, deer; zoo animals such as primates, elephants,zebras, large cats, bears, and the like; research animals such asrabbits, sheep, pigs, dogs, primates, mice, rats and other rodents;avians, including but not limited to chickens, ducks, turkeys, ostrich,and emu; and aquatic animals chosen from fish and crustaceans including,but not limited to, salmon, shrimp, carp, tilapia, and shell fish.

In some aspects, the animal is a livestock animal. The term “livestock”as used herein refers to domesticated animals raised in an agriculturalsetting to produce labor and commodities such as meat, eggs, milk, fur,leather, and wool. The term “livestock” can be used to refer solely toanimals that are bred for consumption. The term can also be used torefer only to farmed mammalian animals, such as cattle, sheep, horses,pigs, and goats. In some aspects, the animal is a pig.

The method orally administers an effective amount of a therapeutic clayto the animal. As used herein, the phrase “effective amount” is used tomean an amount that is intended to qualify the amount of an agent orcompound, that when administered, it will achieve the goal of improvingthe performance of an animal compared to the performance of the animalfed a control diet without the agent or compound.

The timing and duration of administration of the clay of the inventionto an animal can and will vary. For instance, a clay can be administeredroutinely throughout the period when the animal is raised. A clay can beadministered at various intervals. For instance, a clay can beadministered daily, weekly, monthly or over a number of months In someaspects, a clay is administered daily. In other aspects, a clay isadministered weekly. In yet other aspects, a clay is administeredmonthly. A clay can also be administered every three to six months. Asit will be recognized in the art, the duration of treatment can and willvary and can be determined experimentally.

The clay can be administered to the animal in a single dose or a numberof doses throughout the period of administration. For instance, a singledose of the clay can be administered after breeding, once duringgestation, at birth, or once after farrowing. Alternatively, multipledoses of the clay can be administered during gestation, duringlactation, and combinations thereof. For instance, administration of theclay can start after mating and continue to the end of lactation. Insome aspects, the clay is administered from breeding until farrowing.For instance, when the animal is a pig, a clay can be administered threeweeks prior to farrowing, or at day 110, 111, 112, 113, or 114 ofgestation. In some aspects, the clay is administered from farrowinguntil weaning. The clay can also be administered throughout the periodof lactation. In some aspects, the clay is administered throughout theperiods of gestation and lactation.

In some aspects, the clay is administered orally to an animal by addingthe clay to a feed, formulating the clay with the feed, or supplementformulation and feeding the feed or supplement formulation to theanimal. Formulating the clay with a feed can be as described in SectionB above.

When administered to an animal with a feed or supplement formulation,the amount of clay in the feed composition can range from about 0.1lb/ton to 10 about lb/ton. For instance, the amount of clay in a feedcomposition can range from about 0.5 lb/ton to about 2.0 lb/ton.Alternatively, the amount of day in a feed composition can range fromabout 0.4 lb/ton to about 0.6 lb/ton. The amount of clay in a gestationfeed composition can range from about 0.5 lb/ton to about 6.0 lb/ton. Insome aspects, the amount of clay in a gestation feed composition rangesfrom about 0.5 lb/ton to about 4.0 lb/ton. The amount of clay in alactation feed composition can range from about 0.5 lb/ton to about 6lb/ton. In some aspects, the amount of clay in a lactation feedcomposition ranges from about 1 lb/ton to about 2 lb/ton.

As will be appreciated by one of skill in the art, a dose of acomposition of the invention can and will vary depending on the animal,the frequency and timing of administration of the dose, body weight,sex, age and/or medical condition of the animal, the desired growth rateand efficiency, the method of administration, and the duration oftreatment

The rate of administration of the clay of the disclosure may depend onthe level of reducing agent in the clay. For instance, the level ofreducing agent in the clay may be determined before administration toadjust the level of clay that may be used. The oxidation-reductionpotential of the clay can be determined and the level of clay used in amethod, composition, or formulation of the present disclosure isadjusted based on the oxidation-reduction potential of the clay. Theoxidation-reduction potential of the clay can provide a general measureof the therapeutic potential of a clay that may be used irrespective ofthe reducing agents present in the clay. Alternatively, the content ofone or more specific reducing agents in the clay may be determined.

In some aspects, the amount of clay administered to a maternal animalcan range from about 1.0 g/d to about 10 g/d, from about 0.1 g/d toabout 8 g/d, from about 0.5 g/d to about 3 g/d, or from about 4.0 g/d toabout 7 g/d. In some aspects, the amount of clay administered to amaternal animal ranges from about 0.1 g/d to about 5 g/d. The clay canbe administered to an animal during gestation at a rate ranging fromabout 0.5 g/d to about 3 g/d. Alternatively, the clay can beadministered to an animal during lactation at a rate ranging from about4.0 g/d to about 5 g/d. Further, when the animal is a pig, the clay canbe administered starting on about the 1^(st) day to about the 100^(th)of gestation.

Administering a therapeutically effective amount of the clay improvesreproductive performance and litter performance in an animal. As usedherein, the term “reproductive performance” refers to any aspect ofanimal health and wellbeing that could measurably affect reproduction ofthe animal. For instance, reproductive performance can be measured bythe health and vitality of the animal, thereby making the animal morefit for reproduction and for producing healthy animals, the number ofprogeny produced by the animal, and the general health and vitality ofthe progeny produced by the animal. For instance, when a clay isadministered to a sow, the number of pigs born at a weight of less than1.7 lbs can be significantly reduced.

As used herein, the term “litter performance” refers to any aspect ofhealth and wellbeing of a litter of the mother administered the claythat could measurably affect reproduction of the animal. It should benoted that when referring to litter performance after weaning, theimprovement in performance is a result of the administration of the clayto the mother. As such, the litter of an animal administered the claywill have improved performance after weaning when the animal is notadministered the clay.

In some aspects, administration of a therapeutically effective amount ofthe clay improves reproductive performance. Improving reproductiveperformance can comprise reducing embryonic loss, promoting pregnancy,increasing litter size, increasing the number of live births, improvingthe immune status of the maternal animal, reducing the concentration offecal amino acids, reducing the concentration of fecal short-chainedamino acid, and increasing litter birth weight.

Improving the immune status of the maternal animal can comprise anincreased level of IFNγ and TNF-α in the maternal animal, and decreasedlevels of tumor necrosis factor related apoptosis inducing ligand(TRAIL) in the maternal animal. In some aspects, the level ofpre-farrowing TNF-α in the maternal animal is positively correlated withtotal wean, negatively correlated with subsequent stillborns, andpositively correlated with subsequent mummies. In some aspects, thelevel of pre-farrowing TRAIL is negatively correlated with subsequenttotal born and subsequent born alive. In some aspects, the level of weanIFN-γ is positively correlated with total wean.

In some aspects, administration of a therapeutically effective amount ofthe clay improves liter performance. Improving litter performance cancomprise increasing the amount of young animal colostrum intake,reducing young animal pre-weaning mortality, reducing the number ofyoung animals lost due to low viability, reducing the number of weanedyoung animals, improving the immune status of young animals at weaning,reducing the number of lightweight young animals from nursery to market,increasing the number of young animals marketed per sow, and increasingcalculated litter weight gain. The immune status can comprise totalimmunoglobulins in blood.

A. Improving Performance in a Pig.

Another aspect of the disclosure encompasses a method of increasing theamount of piglet colostrum intake, reducing pre-weaning mortality,reducing the number of piglets lost due to low viability, reducing thenumber of weaned pigs, reducing the number of lightweight pigs fromnursery to market, increasing the number of pigs marketed per sow, andincreasing calculated litter weight gain. The method comprises orallyadministering to a sow an effective amount of a therapeutic clay. Insome aspects, the sow is parity 2 or parity 6 or more.

The clay can be as described in Section I(A), and the clay formulationscan be as described in Section I(B) above.

The clay can be administered during gestation, during lactation, andcombinations thereof. For instance, the clay can be administered for aperiod of time during gestation. In some aspects, the clay isadministered from breeding until farrowing. The clay can also beadministered for a period of time during lactation. For instance, theclay can be administered from farrowing until weaning. In some aspects,the clay is administered starting on day 3 to day 93 of gestation.

In some aspects, the amount of clay in a feed composition can range fromabout 0.1 lb/ton to 10 lb/ton. For instance, the amount of clay in agestation feed composition can range from about 0.1 lb/ton to 4.0lb/ton. The amount of clay in a lactation feed composition can rangefrom about 1.0 lb/ton to 2.0 lb/ton.

The amount of clay administered to a sow can range from about 1.0 g/d toabout 10 g/d, from about 0.1 g/d to about 8 g/d, from about 0.5 g/d toabout 3 g/d, or from about 4.0 g/d to about 7 g/d. Further, the clay canbe administered starting three weeks after breeding, or on day 3 to 93of gestation.

An additional aspect of the disclosure encompasses method of reducingembryonic loss, increasing litter size, increasing the number of livebirths, improving the immune status of the sow, reducing theconcentration of sow fecal amino acids, reducing the concentration ofmaternal fecal short-chained amino acid, and increasing litter birthweight. The method comprises orally administering to a sow an effectiveamount of a therapeutic clay. In some aspects, the sow is parity 2 orparity 6 or more.

Yet another aspect of the disclosure encompasses a method of enhancingpig litter performance. The method comprises orally administering aneffective amount of a therapeutic clay to a sow. In some aspects, thesow is parity 2, or parity 6 or more. Enhancing litter performance cancomprise increasing the amount of piglet colostrum intake, reducingpre-weaning mortality, reducing the number of piglets lost due to lowviability, reducing the number of weaned pigs, improving the immunestatus of piglets at weaning, reducing the number of lightweight pigletsfrom nursery to market, increasing the number of pigs marketed per sow,and increasing calculated litter weight gain.

One aspect of the present disclosure encompasses a method of improvingpig litter performance, the method comprising orally administering aneffective amount of a therapeutic clay to a sow. Improving litterperformance can comprise increasing amount of piglet colostrum intake,reducing piglet pre-weaning mortality, reducing the number of pigletslost due to low viability, reducing the number of weaned piglets,improving the immune status of piglets at weaning, reducing the numberof lightweight young animals from nursery to market, increasing thenumber of piglets marketed per sow, and increasing calculated litterweight gain.

Definitions

When introducing elements of the present disclosure, the articles “a,”“an,” “the,” and “said” are intended to mean that there are one or moreof the elements. The use of “or” means “and/or” unless stated otherwise.Furthermore, the use of the term “including”, as well as other forms,such as “includes” and “included”, is not limiting. Also, terms such as“element” or “component” encompass both elements and componentscomprising one unit and elements and components that comprise more thanone subunit unless specifically stated otherwise.

Unless otherwise defined herein, scientific and technical terms used inconnection with the present disclosure shall have the meanings that arecommonly understood by those of ordinary skill in the art. The meaningand scope of the terms should be clear, however, in the event of anylatent ambiguity, definitions provided herein take precedent over anydictionary or extrinsic definition. Further, unless otherwise requiredby context, singular terms as used herein and in the claims shallinclude pluralities, and plural terms shall include the singular.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimits of that range is also specifically disclosed. Each smaller rangebetween any stated value or intervening value in a stated range and anyother stated or intervening value in that stated range is encompassedwithin the invention. The upper and lower limits of these smaller rangescan independently be included or excluded in the range, and each rangewhere either, neither or both limits are included in the smaller rangesis also encompassed within the invention, subject to any specificallyexcluded limit in the stated range. Where the stated range includes oneor both of the limits, ranges excluding either or both of those includedlimits are also included in the invention

As used herein, the terms “about” and “approximately” designate that avalue is within a statistically meaningful range. Such a range can betypically within 20%, more typically still within 10%, and even moretypically within 5% of a given value or range. The allowable variationencompassed by the terms “about” and “approximately” depends on theparticular system under study and can be readily appreciated by one ofordinary skill in the art.

As used herein, “administering” is used in its broadest sense to meancontacting a subject with a composition disclosed herein, provided themethod is a controlled method of administration capable of administeringan accurate amount of clay to the animal.

The phrase “effective amount” is used to mean an amount that is intendedto qualify the amount of an agent or compound, that when administered,it will achieve the goal of improving the performance of an animalcompared to the performance of the animal fed a control diet without theagent or compound.

As used herein, the term “w/w” designates the phrase “by weight” and isused to describe the concentration of a particular substance in amixture or solution.

As used herein, the term “subject” refers to a vertebrate species suchas mammals, birds, reptiles, amphibians, and fish. The vertebratespecies may be an embryo, a juvenile, or an adult. Examples of suitablemammals include, without limit, rodents, companion or domestic animals,livestock, and primates. Non-limiting examples of rodents include mice,rats, hamsters, gerbils, and guinea pigs. Non-limiting examples oflivestock include goats, sheep, swine, cattle, llamas, and alpacas.Suitable primates include, but are not limited to, humans, capuchinmonkeys, chimpanzees, lemurs, macaques, marmosets, tamarins, spidermonkeys, squirrel monkeys, and vervet monkeys. Non-limiting examples ofbirds include chickens, turkeys, ducks, and geese.

As used herein, the terms “companion animal” or “domestic animal” referto an animal typically kept as a pet for keeping in the vicinity of ahome or domestic environment for company or protection, regardless ofwhether the animal is kept indoors or outdoors Non-limiting examples ofcompanion animals or domestic animals include, but are not limited to,dogs, cats, house rabbits, ferrets, and horses.

The terms “isolated,” “purified,” or “biologically pure” refer tomaterial that is substantially or essentially free from components thatnormally accompany it as found in its native state. Purity andhomogeneity are typically determined using analytical chemistrytechniques such as polyacrylamide gel electrophoresis or highperformance liquid chromatography. “Purify” or “purification” in otheraspects means removing at least one contaminant from the composition tobe purified. In this sense, purification does not require that thepurified compound be homogenous, e.g., 100% pure.

As various changes could be made in the above-described cells andmethods without departing from the scope of the invention, it isintended that all matter contained in the above description and in theexamples given below, shall be interpreted as illustrative and not in alimiting sense.

EXAMPLES

All patents and publications mentioned in the specification areindicative of the levels of those skilled in the art to which thepresent disclosure pertains. All patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was specifically and individually indicated to beincorporated by reference.

The publications discussed throughout are provided solely for theirdisclosure before the filing date of the present application. Nothingherein is to be construed as an admission that the invention is notentitled to antedate such disclosure by virtue of prior invention.

The following examples are included to demonstrate the disclosure. Itshould be appreciated by those of skill in the art that the techniquesdisclosed in the following examples represent techniques discovered bythe inventors to function well in the practice of the disclosure. Thoseof skill in the art should, however, in light of the present disclosure,appreciate that many changes could be made in the disclosure and stillobtain a like or similar result without departing from the spirit andscope of the disclosure, therefore all matter set forth is to beinterpreted as illustrative and not in a limiting sense.

Example 1: Relationship Between Pro-Inflammatory Cytokines and LitterSize

Thirty-five sows (17 fed a control diet and 18 fed a diet containingclay) were used to determine the effect feeding clay haspro-inflammatory cytokines. Blood samples were taken on day 113 ofgestation and again on day 18-19 of lactation. Serum samples wereanalyzed to determine the circulating levels of tumor necrosis factoralpha (TNF-α), interferon gamma (INF-Y), and tumor necrosis factorrelated apoptosis inducing ligand (TRAIL). Sow reproductive measures andlitter size were collected from the litter immediately followingtreatment with clay in the diet and from the subsequent litter followingthe treatment litter.

The data was transformed prior to analyses, as the serum cytokine levelswere not normally distributed. Box-Cox transformations were used on theserum cytokine data to create a normal distribution. The data was thenanalyzed to determine mean differences and correlation analyses wasconducted to relate the serum cytokine levels to sow performance data.

Parameter Transformation Pre-farrow IFN-γ {circumflex over ( )}(0.25)Pre-farrow TNF-α {circumflex over ( )}(−0.25) Pre-farrow TRAIL{circumflex over ( )}(−0.25) Wean IFN-γ {circumflex over ( )}(0.25) WeanTNF-α {circumflex over ( )}(−0.25) Wean TRAIL {circumflex over( )}(−0.50)

Sows fed a diet including clay had increased total born, born alive, andnumber of pigs weaned for performance immediately following consumptionof the clay-based diet (Table 1). Additionally, subsequent total bornand born alive was increased for sows fed a clay-based diet compared tosows fed the control diet. Serum IFNY increased and TRAIL decreased forsows fed the clay-based diet compared to sows fed a control diet,suggesting that feeding the clay to sows had a positive effect oncontrolling inflammation and that resulting litter size was increased.

Correlation analyses suggests that increased IFNγ and decreased TRAILwere associated with increased litter size and reduced mummies in boththe immediate and subsequent litter (Table 2). Pre-farrowing TNF-α waspositively correlated with total wean (P=0.0838), negatively correlatedwith subsequent stillborns (P=0.0789), and positively correlated withsubsequent mummies (P=0.0356). Pre-farrow TRAIL was negativelycorrelated with subsequent total born (P=0.0062) and born alive(P=0.0062). Wean IFN-γ was positively correlated with total wean(P=0.0779). Wean TNF-α was negatively correlated with subsequentstillborns (P=0.0482), and positively correlated with subsequent mummies(P=0.0141). Wean TRAIL was negatively correlated with subsequent bornalive (P=0.1067).

TABLE 1 ANOVA analysis to evaluate the differences between sows fed acontrol or a diet including clay during gestation and lactationtherapeutic % Item Control clay SE P-value change # of sows 17 18Current parity 4.2 4.0 0.4 0.76 Total born 16.0 16.5 0.8 0.66 +3.1 Bornalive 14.7 15.3 0.7 0.57 +4.1 Stillborns, % 3.7 4.8 1.2 0.52 +29.7Mummies, % 3.4 2.0 1.2 0.40 −41.2 Total wean 13.0 14.0 0.6 0.21 +7.7Subsequent parity 5.2 5.0 0.4 0.76 Total born 16.9 17.3 0.9 0.76 +2.4Born alive 14.0 14.1 1.1 0.96 +0.7 Stillborns, % 11.7 10.5 3.3 0.79−10.3 Mummies, % 1.1 1.4 0.5 0.69 +27.3 Sow biomarker Pre-farrow IFN-γ,pg/mL 4,099 5,630 1,753 0.41 +37.4 TNF-α, pg/mL 640 737 139 0.44 +15.2TRAIL, pg/mL 56.3 48.8 62.6 0.76 −13.3 At weaning IFN-γ, pg/mL 2,3563,695 2,384 0.41 +56.8 TNF-α, pg/mL 449 488 109 0.70 +8.7 TRAIL, pg/ml39.8 31.3 240.5 0.51 −21.4

TABLE 2 Correlation analysis to evaluate the linear relationship betweensow reproductive performance and biomarkers Pearson CorrelationCoefficients Prob > |r| under H0: Rho = 0 Number of Observations SubPerStill- PerMum- CalTo- SubPer Mum- TB BA born mies talWean SubTB SubBAStillborn mies Pre_IFNgam- 0.15896 0.08215 0.08276 0.16434 0.078240.15975 0.06950 −0.04250 0.13805 matrans 0.361735 0.639035 0.6365350.345535 0.655035 0.407829 0.720229 0.826729 0.475129 Pre_TNFtrans−0.10913 −0.19964 0.15168 0.12651 −0.29644 −0.09729 −0.05160 0.33159−0.39176 0.532635 0.250235 0.384435 0.469035 0.083835 0.615629 0.7904290.078929 0.035629 Pre_TRAILtrans 0.18092 0.10464 0.24253 0.08268 0.160630.49644 0.49575 −0.24728 −0.02925 0.298335 0.549735 0.160435 0.6368350.356635 0.006229 0.006229 0.195929 0.880329 Wean_IFNgam- 0.261560.22978 0.00430 0.08475 0.30193 0.22642 0.07254 −0.01265 0.19577 matrans0.129135 0.184235 0.980535 0.628335 0.077935 0.237629 0.708429 0.9481290.308829 Wean_TNFtrans −0.04202 −0.08152 0.08754 0.04560 −0.11449−0.12353 −0.04353 0.37000 −0.45078 0.810635 0.641535 0.617035 0.7948350.512535 0.523229 0.822629 0.048229 0.014129 Wean_TRAILtrans 0.132480.09820 0.16013 −0.01024 0.03776 0.29289 0.30582 −0.12183 −0.114930.448135 0.574735 0.358135 0.953535 0.829535 0.123129 0.106729 0.5290290.552729

Example 2: Effect of Dietary Clay Fed to Sows Three Weeks Prior toFarrowing Experimental Design, Procedures, and Data Collection AnimalHousing

Sows were individually housed in gestation stalls after mating and fedonce per day based on their respective body condition score via afeed/water trough throughout the gestation period. Water was availableon an ad libitum basis. On approximately d 112 of gestation, sows weremoved to the farrowing barn and placed randomly in farrowing crates.Diets were changed from gestation to lactation diets and were fed adlibitum for the entire lactation period.

Dietary Treatments

Dietary treatments began approximately 93 days after mating. Every 10sows located in the adjacent stalls were considered one subgroup. On thefirst day of the experiment, each subgroup was randomly assigned to oneof 2 treatments with top-dressing of products provided for treatment 2(Table 3). One off-test sow was placed between each subgroup to preventthe mixture of experimental diets. To identify the treatments, eachon-test sow was marked using the spray marker on the corner of their sowID cards according to their assigned color.

TABLE 3 Dietary treatments and assigned colors for sows. Daily Dailyscoop scoop Inclusion size in size in No. of Treatment Additive Rategestation¹ lactation² sows 1. Control None None — — 120 2. ClayTherapeutic 2.0 lb/ton ½ tsp³ 1 tsp³ 120 clay⁴ Total 480 ¹Calcuatedbased on the assumption that the average feed intake is 5.0 lb/day ingestation. ²Calcuated based on the assumption that the average feedintake is 10.0 lb/day in lactation. ³Scoop amounts equated 2.26 g/d and4.52 g/d for gestation and lactation, respectively. ⁴2 lb version(rather than 4 lb version) of therapeutic clay used for the study.

Experimental Diets

Basal diets (Table 4) were standard gestation and lactation dietswithout the addition of betaGRO®, yeast, or other clay-basedtechnologies. Treatment 2 was delivered to sows by top-dressing usingthe designated teaspoons. During the late gestation period, top-dressingwas performed daily by dropping products in front of the feed/watertrough at prescribed rate when feeding in the morning. Aisles are sweptof feed prior to water delivery.

After farrowing and throughout the entire lactation period, top-dressingof products at the rate prescribed for lactation was performed dailyuntil weaning. On the day of weaning, sows were returned to thegestation barn and monitored for days from weaning to estrus.

TABLE 4 Dietary composition of basal diets Ingredient, AF GestationLactation Corn - Fine Ground 1,522.88 1,262.96 Soybean meal 297.45599.22 Dried distillers grains N/A N/A Salt 12.00 12.00 CalciumCarbonate 38% 26.48 15.61 Phosphate - Mono Dicalcium 25.82 23.02 Fat -Fancy Tallow 2.58 71.40 L-Lysine HCL 78.8% N/A 3.24 DL Methionine-Dry99% N/A N/A Threonine N/A 0.71 Tryptophan 100% N/A N/A Phytase 0.28 0.35Tribasic Copper Chloride N/A N/A Sow VTM w/Choline 5.00 5.00 Wheat Midds100.00 N/A Choline Chloride - 60 1.02 N/A SALCURB 6.50 6.50 Total2,000.00 2,000.00 Nutr. Composition Crude Protein, % 13.22 18.70 Fat, %2.66 5.65 SW NE, kcal/kg 2,250.00 2,400.00 Lysine, % 0.65 1.15 SW SI digLys, % 0.57 1.04 Mean Diam, microns 380.72 315.74 Calcium, % 0.81 0.61Phosphorus, % 0.60 0.58 Ca/P Ratio, ratio 1.35 1.05 SW dig P, % 0.410.43 ¹Diets updated 19 May 2016.

Data Collection Reproductive and Litter Performance:

Individual sow body weight was measured (1) on the day sows weretransferred to the farrowing barn, and (2) at weaning. The data was usedto calculate the body weight loss during the lactation period using theformula: Sow BW Loss=Wean−(PRE−(LW+LW/5.5)), where Wean=sow weight atweaning; PRE=sow pre-farrow weight; LW=litter weight; LW/5.5=estimatedplacental weight. Days of lactation and days from weaning to estrus wasrecorded. Sow feed intake was measured during lactation for at least 20sows/treatment (at least 40 sows measured) via Gestal Solo system. Thenumber of piglets born (alive and dead), individual birth weight (aliveand dead), individual weaning weight, and the number of dead pigletsduring lactation were recorded for each litter. Cross-fostering andremoval of unthrifty pigs was allowed within 24 days after birth andonly within treatments or to non-test litters.

Statistical Analysis

Data was analyzed using ANOVA by the MIXED procedure of SAS. Sow/litterserved as the experimental unit. The statistical model included fixedeffect of dietary treatments and a covariate of parity. Multiplecomparisons between treatments were performed using the Tukey adjustmentoption of SAS. All results were reported as least squares means. Thesignificance level chosen was α=0.05. Treatment effect was consideredsignificant if P<0.05, whereas values between 0.05≤P≤0.10 wereconsidered as statistical trends.

Results

Sows fed diets containing clay had greater (P<0.05) number of bornalive, litter birth weight, calculated total wean, calculated litterweaning weight, and calculated litter weight gain without sow BW changecompared to sows fed control diets (Table 5). Sows fed diets containingclay had lower (P<0.05) percent of mummies compared to sows fed thecontrol diets. Sows fed diets containing clay tended (0.05<P<0.10) tohave greater number of total-born pigs and calculated litter weight gainwith sow BW change.

CONCLUSION

The objective of this trial was to determine the effects of feeding clayat 2.0 lb/ton through late gestation and lactation on sow and litterperformance and sow fecal shedding of E. coli compared to sows fed basaldiets. Feeding clay at 2.0 lb/ton had a positive and significant impacton the born alive, mummy percentage, litter birth weight calculatednumber weaned, and calculated litter gain weight. Adding clay to sowdiets did not negatively impact any measurement, and there were notreatment differences in the fecal measurements.

TABLE 5 Effect of feeding clay to sows on reproductive performance ItemControl Clay¹ PSE P-value Reproductive performance of sows # of Sows 10499 N/A N/A Parity 4.6 4.2 0.2 0.28 Total born 13.6 14.5 0.4 0.06 Bornalive 12.4 13.6 0.4 0.02 Stillborn, % 5.4 4.9 0.8 0.59 Mummies, % 3.11.7 0.6 0.03 Litter birth weight, lb 36.2 39.3 1.1 0.02 Pig birthweight,² lb 2.80 2.87 0.05 0.23 Pigs with birth weight < 27.1 26.2 N/A0.61 2.5 lb, % Pre-weaning 6.5 5.9 1.2 0.66 mortality, % Calculatedtotal wean³ 11.6 12.6 0.4 0.02 Lactation length, day 17.7 17.8 0.2 0.55Pig weaning weight,⁴ lb 11.07 11.32 0.18 0.23 CV of pig weaning 20.319.3 N/A 0.96 weight, % Calculated litter 131.2 144.0 4.9 0.02 weaningweight,^(4.5) lb Calculated litter 5.3 5.9 0.2 0.03 weight gain,⁴ lb/day(without sow BW change) Calculated litter weight 5.6 6.3 0.3 0.07 gain(with sow BW change),⁴ lb/day Sow body weight 9.3 13.6 4.0 0.33 change,⁴lb % of sows lost weight 50.0 45.5 N/A 0.64 Wean-estrus intervals⁴ 5.04.5 0.3 0.29 % sows with wean- 4.8 3.0 N/A 0.52 estrus > 7 days Culledsows, % 22.1 14.1 N/A 0.18 Sow lactation feed consumption⁴ # of Sows 2223 N/A N/A % of Sows with feed 21.2 23.2 N/A N/A measurement inlactation Parity 4.7 3.7 0.5 0.17 Lactation length, day 17.8 17.9 0.30.86 ADFI, lb/day 11.35 10.98 0.30 0.35 Fecal measurements of sows # ofSows 30 30 N/A N/A % of Sows with fecal 28.8 30.3 N/A N/A measurementsParity 3.97 4.00 0.42 0.96 Fecal measurements prior to farrow Total E.coli., log cfu/g 7.64 7.53 0.16 0.51 ETEC, log cfu/g 6.64 6.21 0.72 0.57F18.⁶ log cfu/g 0.00 0.00 N/A N/A Total Clostridia, log 7.65 7.82 0.110.13 cfu/g C. perfringens Type A, 5.27 6.48 0.93 0.22 log cfu/g Fecalmeasurements at weaning Total E. coli, log cfu/g 6.67 6.25 0.29 0.22ETEC, log cfu/g 3.94 3.09 0.75 0.32 F18,⁷ log cfu/g 0.04 0.38 0.47 0.52Total Clostridia, log 6.32 6.14 0.33 0.63 cfu/g C. perfringens Type A,4.33 5.07 0.77 0.40 log cfu/g ¹Clay was top-dressed at 2 lb/ton ofcomplete feed in gestation and lactation. Top dressing started at day 93of gestation and continued through entire lactation. ²Number of bornalive was used as covariate in the statistical model ³Calculated totalwean = born alive × (1-PWM/100) ⁴Lactation length was used as covariatein the statistical model ⁵Calculated litter weaning weight = pig weaningwt × calculated total wean ⁶None of the samples had a detectable levelof F18 count ⁷One sample from Control treatment and three samples fromClay treatment had a detectable level of F18 count

Example 3: Effect of Adding Clay to Sow Diets During Gestation andLactation on Reproductive and Litter Performance Experimental Design,Procedures, and Data Collection Animal Housing

Sows were individually housed in gestation stalls after mating and fedonce per day based on their respective body condition score via afeed/water trough throughout the gestation period. Water was availableon an ad libitum basis. On approximately d 112 of gestation, sows weremoved to the farrowing barn and placed randomly in farrowing crates.Diets were changed from gestation to lactation diets and were fed adlibitum for the entire lactation period.

Dietary Treatments

Dietary treatments began approximately 94 days after mating. Every 10sows located in the adjacent stalls were considered one subgroup. On thefirst day of the experiment, each subgroup was randomly assigned to oneof 4 treatments with top-dressing of products provided for treatments 2through 4 (Table 6). One off-test sow was placed between each subgroupto prevent the mixture of experimental diets.

TABLE 6 Dietary treatments and assigned colors for sows. Inclusion No.of Treatment Additive Rate sows 1. Control None None 120 2. Clay_0.5Clay³ 0.5 lb/ton 120 3. Clay_1.0 Clay³ 1.0 lb/ton 120 4. Clay_1.5 Clay³1.5 lb/ton 120 480 ¹Calculated based on the assumption that the averagefeed intake is 5.0 lb/day in gestation. ²Calculated based on theassumption that the average feed intake is 10.0 lb/day in lactation. ³2lb version (rather than 4 lb version) of therapeutic clay used for thestudy.

Experimental Diets

Basal diets (Table 7) were standard gestation and lactation diets.Treatments 2 through 4 were delivered to sows by top-dressing using thedesignated teaspoons. During the late gestation period, top-dressing wasperformed daily by dropping products in front of the feed/water troughat prescribed rate when feeding in the morning. Aisles are swept of feedprior to water delivery.

After farrowing and throughout the entire lactation period, top-dressingof products at the rate prescribed for lactation was performed dailyuntil weaning. On the day of weaning, sows were returned to thegestation barn and monitored for days from weaning to estrus.

TABLE 7 Dietary composition of basal diets Gestation LactationIngredient, lb Diet¹ Diet¹ Corn 1397.44 1016.28 Distillers dried grains265.83 352.54 Soybean meal 104.26 479.56 Salt 10.55 10.05 Phosphate -Mono Dicalcium 21.89 17.12 Calcium carbonate 22.57 19.57 L-lysine HCL78.8% 5.04 5.92 Choline Chloride - 60 3.17 1.22 Sow VTM w/Choline 5.005.00 Phytase 0.30 0.30 Wheat Midds 157.45 — Fat - corn oil — 85.94 SALCURB 6.50 6.50 Total 2000.00 2000.00 Calculated nutrient compositionCrude Protein, % 12.87 20.51 Fat, % 3.24 7.21 SW NE, kcal/kg 2210.002400.00 Lysine, % 0.69 1.22 SW SI dig Lys, % 0.57 1.05 Mean Diam,microns 385.69 280.49 Ca, % 0.81 0.75 P. % 0.60 0.56 Ca/P Ration 1.351.35 SW dig P, % 0.46 0.44 ¹Diets included 400 ppm CTC and 35 ppmDenagard.

Data Collection Reproductive and Litter Performance:

Individual sow body weight was measured (1) on the day sows weretransferred to the farrowing barn, and (2) at weaning. The data was usedto calculate the body weight loss during the lactation period using theformula: Sow BW Loss=Wean−(PRE−(LW+LW/5.5)), where Wean=sow weight atweaning; PRE=sow pre-farrow weight; LW=litter weight; LW/5.5=estimatedplacental weight (Fahmy, 1971). Days of lactation and days from weaningto estrus was recorded. Sow feed intake was measured during lactationfor at least 20 sows/treatment (at least 80 sows measured) via GestalSolo system. The number of piglets born (alive and dead), individualbirth weight (alive and dead), individual weaning weight, and the numberof dead piglets during lactation were recorded for each litter.Cross-fostering and removal of unthrifty pigs was allowed within 24 daysafter birth and only within treatments or to non-test litters. Creepfeeding was not offered during this trial, but access to the sow feedwas not restricted.

Statistical Analysis

Data was analyzed using ANOVA by the MIXED procedure of SAS. Sow/litterserved as the experimental unit. The statistical model included fixedeffect of dietary treatments and a covariate of parity. Multiplecomparisons between treatments were performed using the Tukey adjustmentoption of SAS. All results were reported as least squares means. Thesignificance level chosen was α=0.05. Treatment effect was consideredsignificant if P<0.05, whereas values between 0.05≤P≤0.10 wereconsidered as statistical trends.

Results

Sows fed increasing levels of clay had a linear improvement in birthweight (P<0.10; Table 8). Preweaning mortality was reduced P<0.06) insows fed 1 lb/ton, and feed intake (P=0.06) compared to sows fed 0.5lb/ton. Feed intake was increased (P=0.06) during lactation for sows fed1.5 lb of clay/ton, and overall intake increased linearly (P<0.005) asthe inclusion of clay increased in the diet.

Sows fed diets containing clay at 0.5 lb/ton had a lower (P=0.02) cullrate compared to Control sows. Sows fed diets containing clay at 0.5lb/ton tended (0.05<P<0.10) have a lower cull rate compared to sows feddiets containing clay at 1.0 lb/ton and was lower (P=0.02) than sows feddiets containing clay at 1.5 lb/ton.

Example 4: Feeding Clay to Sows Improves Litter Size at Birth and atWeaning

The effect of feeding Clay to sows during gestation and lactation wasevaluated to determine the effect on reproductive performance. Sows(parity≥2) were randomly selected from a commercial herd were allottedto either a Control diet (CON) or a diet containing Clay at 4.0 lb/ton,resulting in 97 sows for CON and 95 sows for Clay treatment. Dietarytreatments started on day 3 after breeding and continued to the end oflactation through top-dressing clay to the basal diet (Table 8 and 9).Individual sow body weight was measured on the day when sows weretransferred to the farrowing crate and at weaning to calculate bodyweight change during lactation period using the formula Sow BWChange=Wean−(PRE−(LW+LW/5.5)), where Wean=sow weight at weaning; PRE=sowpre-farrow weight; LW=litter weight; LW/5.5=estimated placental weight.Lactation length and wean to estrus interval were recorded. The numberof piglets born (alive and dead), individual pig birth weight (alive anddead), individual pig weaning weight, and the number of piglets deadduring lactation were recorded for each litter. Cross-fostering and pullof starves were allowed within 2 days after birth and only withintreatments or to the non-test litters. In addition, piglet management,including tail docking, iron injection, male piglet castration, wereperformed. Piglets' access to the sow feed was not restricted.

TABLE 8 Effect of clay titration on sow and litter performance P-valuesTreatment, lb/ton P- P- Item Control 0.5 1.0 1.5 PSE overall P-linearquadratic # Total Litters 107 114 107 112 N/A N/A N/A N/A Total born perlitter 14.6 14.8 14.1 14.4 0.5 0.49 0.35 0.83 Born alive per litter 13.514.0 13.3 13.6 0.5 0.44 0.57 0.53 % Stillborns 4.1 2.7 2.9 3.1 1.0 0.430.42 0.29 % Mummies 2.7 2.4 2.2 2.1 0.7 0.83 0.39 0.39 Litter birth wt,lb 38.3 39.7 38.4 39.2 1.2 0.53 0.80 0.80 Pig birth wt (adj for born2.88 2.91 2.92 2.96 0.06 0.59 0.16 0.69 alive), lb Measurement of feedintake during lactation # Sows measured 23 25 32 25 N/A N/A N/A N/ALactation days of sows 19.0 18.5 18.1 18.3 0.3 0.12 N/A N/A measured,day ADFI of sows measured, 11.92 12.88 12.69 13.18 0.43 0.09 0.03 0.53lb/day At Weaning Calculated total wean per 12.9 13.1 12.9 12.9 0.4 0.930.68 0.41 litter % PWM 4.2 5.9 3.2 5.0 1.2 0.08 0.99 0.65 Lactationdays, day 18.0 18.6 18.4 18.2 0.2 0.07 N/A N/A Litter weaning wt (adj134.1 132.2 135.7 130.4 3.5 0.36 0.56 0.15 for lactation days), lbLitter weight gain/day, lb 5.2 5.1 5.3 4.9 0.2 0.23 0.46 0.19 Pigweaning wt (adj for 12.5 12.4 12.5 12.3 0.2 0.68 0.47 0.38 lactationdays), lb Wean-estrus intervals, d 4.6 5.1 4.4 4.5 0.5 0.30 0.40 0.61 %Culled Sows 11.2 2.6 8.4 10.7 N/A 0.09 N/A N/A Sow BW change during 3.22.2 5.7 9.3 5.5 0.48 0.19 0.37 lactation, lb Percentage of sow BW 0.80.6 1.1 1.8 0.9 0.52 0.22 0.34 change during lactation, %

Example 4: Effect of Feeding Clay to Sows in Gestation and Lactation onLitter Performance Experimental Design, Procedures, and Data CollectionAnimal Housing

Sows were individually housed in gestation stalls after mating and fedonce per day based on their respective body condition score via afeed/water trough throughout the gestation period. Water was availableon an ad libitum basis. On approximately d 112 of gestation, sows weremoved to the farrowing barn and placed randomly in farrowing crates.Diets were changed from gestation to lactation diets and were fed adlibitum for the entire lactation period.

Dietary Treatments

Dietary treatments began approximately 3 days after mating. Every 10sows located in the adjacent stalls were considered one subgroup. On thefirst day of the experiment, each subgroup was randomly assigned to oneof 4 treatments with top-dressing of products provided for treatments 2through 4 (Table 9). One off-test sow was placed between each subgroupto prevent the mixture of experimental diets.

TABLE 9 Dietary treatments and assigned colors for sows. InclusionTreatment Additive Rate No. of sows 1. Control None — 101 2. Claytherapeutic 2.0 lb/ton³ 105 clay 3. phytogenic Phytogenic 0.4 lb/ton⁴105 4. Clay + therapeutic 2.0 lb/ton + 95 phytogenic clay + 0.4 lb/ton,phytogenic resp. Total 406 ¹Calculated based on the assumption that theaverage feed intake is 5.0 lb/day in gestation. ²Calculated based on theassumption that the average feed intake is 10.0 lb/day in lactation. ³NQtherapeutic clay ore was given at a daily inclusion of rate 2.27 g/day +1:1 inclusion of ground corn (total 4.54 g/day) during gestation.⁴Phytogenic was given at a daily inclusion rate of 0.45 g/day + 1:1inclusion of ground corn (total 0.90 g/day) during gestation.

Experimental Diets

Basal diets were standard gestation and lactation diets used by NHF(Table 10A and Table 10B). Treatments 2 through 4 were delivered to sowsby top-dressing using the designated teaspoons/tablespoons. During thegestation period, top-dressing was performed daily by dropping productsin front of the feed/water trough at prescribed rate when feeding in themorning. Aisles are swept of feed prior to water delivery.

After farrowing and throughout the entire lactation period, top-dressingof products at the rate prescribed for lactation was performed dailyuntil weaning. On the day of weaning, sows were returned to thegestation barn and monitored for days from weaning to estrus.

TABLE 10A Dietary composition of basal diets until Ingredient Gestation¹Lactation² Corn - Fine Ground 1,014.51 1,214.08 Soybean meal 60.00619.87 Distillers dried grains 800.00 N/A Salt 12.00 12.00 CalciumCarbonate 38% 34.21 24.81 Fat - Fancy Tallow N/A 85.85 L-Lysine HCL78.8% 7.56 5.88 DL Methionine-Dry 99% N/A N/A Threonine 0.23 0.68Tryptophan 100% 0.36 N/A Phytase 0.35 0.35 Tribasic Copper Chloride N/AN/A Sow VTM w/Choline 5.00 5.99 TIAMULIN 10 g/lb N/A 3.50 CTC-AUREOMY-90g/lb N/A 4.40 SALCURB 6.50 6.50 Thiamine 10 Gr/Lb 0.45 N/A Feed Aid 3.00N/A Sow Platform N/A N/A Phosphate - Mono Dicalcium 11.87 23.99 WheatMidds 43.98 N/A Amount Per Ton 2,000.00 2,000.00 Cost/Ton ($, As Fed)140.71 211.44 Nutrient, As Fed Conc Crude Protein, % 16.48 18.81 Fat, %3.91 6.23 Mean Diam, microns 253.63 303.52 Calcium, % 0.81 0.80Phosphorus, % 0.60 0.60 Ca/P Ratio, ratio 1.35 1.35 SW dig P, % 0.490.44 SW NE, kcal/kg 2,156.32 2,400.00 Lysine, % 0.82 1.26 SW SI dig Lys,% 0.69 1.15 Added Salt, % 0.60 0.60 Calcium for Tag, % 0.80 0.80¹Gestation diets updated October 2017 ²Lactation diets updated November2017. CTC and Denagard provided during lactation at 400 g and 35 g,respectively.

TABLE 10B Dietary composition of basal diets beginning Apr. 2, 2018.Ingredient Gestation¹ Lactation² Corn - Fine Ground 1,012.51 1,214.08Soybean meal 60.00 619.87 Distillers dried grains 800.00 N/A Salt 12.0012.00 Calcium Carbonate 38% 34.21 24.81 Fat - Fancy Tallow N/A 85.85L-Lysine HCL 78.8% 7.56 5.88 DL Methionine-Dry 99% N/A N/A Threonine0.23 0.68 Tryptophan 100% 0.36 N/A Phytase 0.35 0.35 Tribasic CopperChloride N/A N/A Sow VTM w/Choline 5.00 5.99 TIAMULIN 10 g/lb N/A 3.50CTC-AUREOMY-90 g/lb N/A 4.40 SALCURB 6.50 6.50 Thiamine 10 Gr/Lb 0.45N/A Feed Aid N/A N/A Defusion Plus 5.00 N/A Phosphate - Mono Dicalcium11.87 23.99 Wheat Midds By-Product 27-34% NDF 43.98 N/A Amount Per Ton2,000.00 2,000.00 Cost/Ton ($, As Fed) 140.71 211.44 Nutrient, As FedConc Crude Protein. % 16.48 18.81 Fat, % 3.91 6.23 Mean Diam, microns253.63 303.52 Calcium, % 0.81 0.80 Phosphorus, % 0.60 0.60 Ca/P Ratio,ratio 1.35 1.35 SW dig P, % 0.49 0.44 SW NE, kcal/kg 2,156.32 2,400.00Lysine, % 0.82 1.26 SW SI dig Lys, % 0.69 1.15 Added Salt, % 0.60 0.60Calcium for Tag, % 0.80 0.80 ¹Gestation diets updated April 2018.²Lactation diets updated November 2017. CTC and Denagard provided duringlactation at 400 g and 35 g. respectively.

Data Collection Reproductive and Litter Performance:

Individual sow body weight was measured (1) on the day sows weretransferred to the farrowing barn, and (2) at weaning. The data was usedto calculate the body weight loss during the lactation period using theformula: Sow BW Loss=Wean−(PRE−(LW+LW/5.5)), where Wean=sow weight atweaning; PRE=sow pre-farrow weight, LW=litter weight; LW/5.5=estimatedplacental weight (Fahmy. 1971). Days of lactation and days from weaningto estrus was recorded. The number of piglets born (alive and dead),individual birth weight (alive and dead), individual weaning weight, andthe number of dead piglets during lactation were recorded for eachlitter. Cross-fostering and removal of unthrifty pigs was allowed within24 days after birth and only within treatments or to non-test litters.Lactation feed intake was monitored for a subset of sows with JygaGestal Solo® electronic sow feeders.

Samples:

Collected blood samples from sows prior to farrow and at weaning from 25sows/treatment. Day of gestation and lactation were recorded for eachsampling sow. Sow parities were balanced into 3 subgroups: P2-4, 5-7,and 8+. Collected blood samples from 2 piglets (gilt and barrow) at day2 of age and at weaning and 25 litters/treatment. Age and individualweights at collection were recorded. Colostrum samples were collectedfrom Treatments 1 and 4 (25 sows/treatment) within 24 hours offarrowing. Colostrum samples were not analyzed at this time.

Statistical Analysis

Data was analyzed using ANOVA by the MIXED procedure of SAS. Sow/litterserved as the experimental unit. The statistical model included fixedeffect of dietary treatments and a covariate of parity. Multiplecomparisons between treatments were performed using the Tukey adjustmentoption of SAS. All results were reported as least squares means. Thesignificance level chosen was α=0.05. Treatment effect was consideredsignificant if P<0.05, whereas values between 0.05≤P≤0.10 wereconsidered as statistical trends.

Results

Sows fed clay had increased (P<0.05) number of total-born pigs, liveborn pigs and heavier birth weights than the control fed sows (Table11). The number of pigs born less than 1.7 lbs was reduced (P<0.05) forsows fed clay compared to sows fed a control diet. The number ofabortions was reduced (P<0.05) for sows fed clay compared to sows fedthe control diet. The improvements in total pigs born alive for sows fedclay-based diets resulted in increased number of pigs weaned as well.

TABLE 11 Summary 2017-006 therapeutic clay × phytogenic long term sowstudy Main effect of No therapeutic clay Main effect therapeutictherapeutic No of phytogenic clay clay thera- thera- No No No peuticpeutic phyto- phyto- phyto- phyto- phyto- phyto- Item clay clay genicgenic genic genic genic genic # of 206 200 206 200 101 105 105 95 SowsParity¹ 5.0 5.0 5.1 4.9 5.1 4.8 5.0 5.0 Con- 98.1 97.7 97.3 98.5 97.798.5 96.9 98.5 ception rate, % Farrow- 90.8 88.1 88.5 90.4 87.7^(c)93.8^(d) 89.2^(cd) 86.9^(c) ing rate, % Culled 2.3 5.4 4.6 3.1 3.8^(ab)0.8^(a) 5.4^(b) 5.4^(b) sows due to vaginal dis- charge, % Sows 3.1 1.51.2 3.5 2.3^(b) 3.8^(b) 0.0^(a) 3.1^(b) aborted, % Reproductiveperformance Total 14.1 14.7 14.4 14.4 13.7^(a) 14.4^(ab) 15.0^(b)14.4^(ab) born Born 13.1 13.7 13.4 13.4 12.8^(a) 13.3^(ab) 13.9^(b)13.5^(ab) alive² Still- 4.0 4.3 4.1 4.2 3.5 4.5 4.7 3.8 borns, % Mum-2.9 2.3 2.4 2.8 2.6 3.3 2.2 2.4 mies, % Total 7.0 6.5 6.5 7.0 6.1 7.86.9 6.1 of still- borns and mum- mies, % Litter 39.5 41.4 40.4 40.538.8^(a) 40.34^(ab) 42.1^(b) 40.8^(ab) birth weight, lb Pig 2.99 3.063.02 3.04 2.97 3.01 3.06 3.06 birth weight, lb Percen- 6.1 5.5 5.7 5.96.6^(a) 5.6^(ab) 4.9^(a) 6.3^(ab) tage of pigs with birth weight < 1.7lb, % Pre- 8.7 8.9 8.6 8.9 8.6 8.8 8.7 9.1 weaning mor- tality, %Piglets 3.2 2.8 3.2 2.8 3.4 3.0 3.0 2.6 dead due to low viability %Calcu- 11.9 12.4 12.2 12.2 11.6^(a) 12.1^(ac) 12.7^(a) 12.2^(ab) latedtotal wean Lac- 19.3 19.1 19.2 19.3 19.2 19.5 19.1 19.1 tationlength^(a) day Pig 12.4 12.1 12.2 12.3 12.3 12.4 12.1 12 1 wean- ingweight lb Litter 146.1 149.2 147.6 147.6 143.7 148.5 151.6 146.8 wean-ing weight, lb Wean- 4.8 4.9 4.7 5.0 4.7 4.9 4.8 5.1 estrus inter- vals,day Sow 12.6 7.7 9.4 10.9 15.3ª 10.0^(ab) 3.6^(a) 11.7^(ab) BW changeduring lac- tation, lb Sow 2.5 1.5 1.9 2.1 3.0^(a) 1.9^(ab) 0.9^(b)2.2^(ab) BW change during lac- tation, % Sow 562 569 567 564 560 563 573564 body weight prior to farrow, lb Sow 525 525 525 524 527 523 524 525body weight at wean- ing, lb % of 34.5 39.5 38.3 35.5 29.7^(a) 39.0^(ac)46.7^(a) 31.6^(ab) sows lost weight Sow feed intake during lactation #of 48 65 57 56 24 24 33 32 Sows meas- ured ADFi 14.7 14.3 14.4 14.5 14.814.6 14.1 14.5 during lac- tation, lb/day Sow 11 0.3 −0.5 1.9 1.9 0.2−3.0 3.7 BW change during lac- tation, lb Sow 0.3 0.1 0.0 0.4 0.5 0.1−0.4 0.6 BW change during lac- tation, % Sow 561 568 567 562 555 566 579557 body weight prior to farrow, lb Sow 513 515 514 514 509 517 519 512body weight at wean- ing, lb Piglet Immunocrit ratio At birth 0.0380.038 0.036 0.040 0.039^(ab) 0.037^(ab) 0.032^(a) 0.043^(c) At 0.0480.050 0.052 0.046 0.050 0.046 0.054 0.046 wean- ing ADG, 0.52 0.51 0.520.51 0.54 0.50 0.50 0.52 lb/day Piglet serum cytokines At birth IFN-α,N/A N/A N/A N/A 0.7 N/A 1.0 N/A pg/mL IL-1β, N/A N/A N/A N/A 19.7 N/A66.0 N/A pg/mL IL-6, N/A N/A N/A N/A 77.7 N/A 218.2 N/A pg/ml IL-8, N/AN/A N/A N/A 37.2 N/A 67.5 N/A pg/mL IL-12, N/A N/A N/A N/A 142 2 N/A162.9 N/A pg/ml TNF-α, N/A N/A N/A NA 7.9 N/A 24.7 N/A pg/mL At weaningIFN-α, N/A N/A N/A N/A 1.3 N/A 1.8 N/A pg/mL IL-1β, N/A N/A N/A N/A 1.8N/A 6.6 N/A pg/mL IL-6, N/A N/A N/A N/A 13.2 N/A 33.3 N/A pg/ml IL-8,N/A N/A N/A N/A 67.4 N/A 75.1 N/A pg/mL IL-12, N/A N/A N/A N/A 488.7 N/A593.6 N/A pg/ml TNF-α, N/A N/A N/A N/A 2.0 N/A 2.3 N/A pg/mL P-valuetherapeutic therapeutic clay × Item PSE clay phytogenic phytogenic # ofN/A N/A N/A N/A Sows Parity¹ 0.2 0.90 0.43 0.45 Con- N/A N/A N/A N/Aception rate, % Farrow- N/A N/A N/A N/A ing rate, % Culled N/A N/A N/AN/A sows due to vaginal dis- charge, % Sows N/A N/A N/A N/A aborted, %Reproductive performance Total 0.4 0.05 0.84 0.04 born Born 0.3 0.020.91 0.11 alive² Still- 0.7 0.72 0.96 0.11 borns, % Mum- 0.5 0.15 0.360.62 mies, % Total 0.9 0.57 0.57 0.13 of still- borns and mum- mies, %Litter 1.0 0.02 0.89 0.10 birth weight, lb Pig 0.05 0.12 0.65 0.62 birthweight, lb Percen- N/A N/A N/A N/A tage of pigs with birth weight < 1.7lb, % Pre- 1.0 0.86 0.72 0.92 weaning mor- tality, % Piglets 0.7 0.480.48 0.99 dead due to low viability % Calcu- 0.3 0.02 1.00 0.10 latedtotal wean Lac- 0.3 0.36 0.62 0.67 tation length^(a) day Pig 0.2 0.130.74 0.96 wean- ing weight, lb Litter 4.5 0.40 1.00 0.19 wean- ingweight, lb Wean- 0.4 0.67 0.38 0.96 estrus inter- vals, day Sow 3.5 0.090.62 0.02 BW change during lac- tation, lb Sow 0.6 0.09 0.76 0.03 BWchange during lac- tation, % Sow 6 0.14 0.56 0.19 body weight prior tofarrow, lb Sow 5 0.97 0.73 0.60 body weight at wean- ing, lb % of N/AN/A N/A N/A sows lost weight Sow feed intake during lactation # of N/AN/A N/A N/A Sows meas- ured ADFi 0.33 0.11 0.67 0.25 during lac- tation,lb/day Sow 5.1 0.59 0.34 0.60 BW change during lac- tation, lb Sow 0.90.69 0.35 0.60 BW change during lac- tation, % Sow 10 0.39 0.54 0.06body weight prior to farrow, lb Sow 9 0.80 0.93 0.32 body weight atwean- ing, lb Piglet Immunocrit ratio At birth 0.004 0.84 0.05 0.01 At0.002 0.24 0.02 0.36 wean- ing ADG, 0.02 0.49 0.70 0.09 lb/day Pigletserum cytokines At birth IFN-α, 2.2 0.15 N/A N/A pg/mL IL-1β, 118.7 0.06N/A N/A pg/mL IL-6, 719.8 0.13 N/A N/A pg/ml IL-8, 12.3 0.01 N/A N/Apg/mL IL-12, 84.9 0.70 N/A N/A pg/ml TNF-α, 338.2 0.03 N/A N/A pg/mL Atweaning IFN-α, 1.0 0.17 N/A N/A pg/mL IL-1β, 41.7 0.001 N/A N/A pg/mLIL-6, 608.5 0.07 N/A N/A pg/ml IL-8, 10.0 0.57 N/A N/A pg/mL IL-12, 72.90.27 N/A N/A pg/ml TNF-α, 60.0 0.03 N/A N/A pg/mL

Example 5: Effect of Clay-Based Diets on Sow Performance by Parity

Sow performance data was reanalyzed to determine the response to feedingclay to sows based on parity (Table 12). Sows were sorted into 6different parity groups; parity 2, 3, 4 & 5, 6 & 7, and 8 or greater.These data suggest that parity had a major impact on the level ofresponse. Parity 2 sows and sows greater than 6 had a more pronouncedimprovement in total born and born alive compared to sows from parity 3,4, and 5. These are usually parities that tend to result in lowerperformance due to health issues in parity 2 sows and age/health effectsin parity 6 sows or older. The data suggest that adding clay to thediets is actually restoring performance to greater levels and improvingthe overall output of the sow herd.

TABLE 12 Effect of parity on the response to feeding clay-based dietsfor the entire gestation + lactation period in sows All Sows Parity = 2Parity = 3 thera- thera- thera- peutic P- peutic P- peutic P- ItemControl clay PSE value Control clay PSE value Control clay PSE value #of Trials 1 1 1 1 1 1 # of Sows 101 105 8 9 13 23 Parity 5.1 5.0 0.20.64 Total born 13.7 15.0 0.4 0.005 14.4 17.3 1.1 0.05 16.6 15.7 0.80.32 Born alive 12.8 13.9 0.3 0.005 13.0 15.7 1.0 0.02 15.8 14.7 0.80.19 Stillborns, 3.5 4.7 0.7 0.17 6.2 8.0 2.1 0.66 3.4 3.5 1.6 0.99 %Mummies, 2.6 2.2 0.5 0.55 1.6 1.2 1.5 0.75 1.3 2.9 1.2 0.24 % Total of6.1 6.9 0.9 0.46 7.8 9.2 2.7 0.75 4.7 6.3 2.1 0.47 stillborns andmummies, % Litter birth 38.8 42.1 1.0 0.003 40.6 49.9 2.8 0.005 49.946.7 2.2 0.16 weight, lb Pig birth 2.97 3.06 0.05 0.12 3.09 3.32 0.150.12 3.34 3.26 0.12 0.47 weight, lb Pre- 8.6 8.7 1.0 0.83 11.5 8.8 2.90.68 7.4 6.7 2.3 0.77 weaning mortality, % Total 11.6 12.7 0.3 0.00711.3 14.2 0.9 0.009 14.6 13.7 0.7 0.25 number of piglet weaned Pig 12.312.1 0.2 0.44 11.3 12.0 0.6 0.52 12.7 12.2 0.5 0.47 weaning weight, lbLitter 143.7 151.6 4.5 0.13 126.7 171.8 12.3 0.05 185.8 167.2 9.6 0.17weaning weight, lb Wean- 4.7 4.8 0.4 0.98 7.6 4.4 1.1 0.18 4.2 5.7 0.90.35 estrus intervals, day Sow BW 15.3 3.6 3.5 0.04 8.5 −0.9 9.8 0.531.8 −1.1 7.5 0.73 change during lactation, lb Parity = 4 & 5 Parity = 6& 7 thera- thera- peutic P- peutic P- Item Control clay PSE valueControl clay PSE value # of Trials 1 1 1 1 # of Sows 33 31 37 23 ParityTotal born 15.7 16.1 0.5 0.44 14.1 16.3 0.5 0.03 Born alive 14.3 15.30.5 0.12 13.2 14.7 0.4 0.07 Stillborns, 4.5 3.6 1.0 0.62 3.5 5.5 1.00.19 % Mummies, 3.5 1.5 0.8 0.07 2.4 3.3 0.7 0.49 % Total of 8.0 5.3 1.30.15 5.9 8.8 1.2 0.17 stillborns and mummies, % Litter birth 42.8 43.51.4 0.53 37.3 42.9 1.3 0.01 weight, lb Pig birth 3.03 2.98 0.08 0.872.79 3.02 0.07 0.07 weight, lb Pre- 7.3 8.2 1.4 0.64 9.3 9.1 1.3 0.94weaning mortality, % Total 13.4 14.2 0.4 0.19 11.9 13.3 0.4 0.06 numberof piglet weaned Pig 12.2 12.6 0.3 0.21 12.3 11.4 0.3 0.08 weaningweight, lb Litter 160.8 171.6 6.1 0.09 145.0 149.1 5.7 0.67 weaningweight, lb Wean- 4.6 4.2 0.6 0.35 3.9 4.3 0.5 0.13 estrus intervals, daySow BW 20.4 6.4 4.7 0.05 15.6 15.0 4.5 0.94 change during lactation, lbParity ≥ 8 thera- peutic P- Item Control clay PSE value # of Trials 1 1# of Sows 10 19 Parity Total born 12.3 14.4 1.0 0.02 Born alive 11.613.3 0.9 0.04 Stillborns, 1.3 5.9 1.9 0.01 % Mummies, 3.2 1.4 1.4 0.30 %Total of 4.5 7.3 2.4 0.20 stillborns and mummies, % Litter birth 32.839.7 2.5 0.004 weight, lb Pig birth 2.68 2.95 0.14 0.05 weight, lb Pre-6.3 9.1 2.6 0.31 weaning mortality, % Total 9.8 11.5 0.8 0.10 number ofpiglet weaned Pig 11.9 11.4 0.5 0.26 weaning weight, lb Litter 131.9139.5 11.0 0.41 weaning weight, lb Wean- 3.8 5.0 1.0 0.43 estrusintervals, day Sow BW 15.0 −0.9 8.5 0.22 change during lactation, lb

Example 6: Effect on Sows with Larger Litters

The data was re-analyzed in example 6 to determine the effectiveness offeeding clay-based diets to sows with greater than 15.5 pigs born alive(Table 13). These data suggest that born alive increased by 2% and thatthe number of pigs weaned increased by 0.7 pigs per litter (P=0.13).These data further illustrate that the effects of increasing litter sizeis not a function of lower sow performance (>15.5 pigs total born). Evenin larger litter sizes feeding clay in gestation and lactation dietsresults in more pigs weaned.

TABLE 13A Meta-analysis for feeding clay-based diets to high prolificsows for the entire gestation + lactation Meta-analysis therapeutic P-Item Control clay PSE value # of Trials 2 2 # of Sows 105 129 Parity 5.35.1 0.2 0.47 Total born 16.9 17.2 0.2 0.28 Born alive 15.7 16.0 0.2 0.22Stillborn, % 3.8 4.1 0.5 0.74 Mummies, % 3.3 2.9 0.5 0.55 Stillborns +7.1 7.0 0.7 0.90 Mummies, % Litter birth 44.7 45.2 0.7 0.57 weight, lbPig birth 2.85 2.86 0.04 0.87 weight, lb Pre-weaning 11.3 10.7 1.2 0.43mortality, % Total 13.3 14.0 0.2 0.13 number of piglets weaned Pigweaning 12.0 12.0 0.1 0.88 weight, lb Litter 168.6 172.6 3.0 0.34weaning weight, lb Sow body 7.0 0.2 2.8 0.09 weight change, lbWean-estrus 4.7 4.6 0.4 0.50 intervals

TABLE 13B Meta-analysis for feeding clay-based diets to high prolificsows for the entire gestation + lactation Parity = 2 Parity = 3 P-therapeutic P- Item Control PSE value Control clay PSE value Control #of Trials 2 2 2 2 # of Sows 105 9 22 14 Parity 5.3 0.2 0.47 Total born16.9 0.2 0.28 16.9 17.3 0.5 0.57 17.3 Born alive 15.7 0.2 0.22 15.5 16.00.5 0.49 16.3 Stillborn, % 3.8 0.5 0.74 5.6 4.8 1.5 0.71 2.8 Mummies, %3.3 0.5 0.55 2.1 2.2 1.2 0.94 2.7 Stillborns + 7.1 0.7 0.90 7.7 7.1 1.90.82 5.4 Mummies, % Litter birth 44.7 0.7 0.57 47.3 47.4 1.8 0.97 50.1weight, lb Pig birth 2.85 0.04 0.87 3.02 2.98 0.10 0.76 3.13 weight, lbPre-weaning 11.3 1.2 0.43 9.7 11.7 1.9 0.31 8.1 mortality, % Total 13.30.2 0.13 14.4 13.7 0.4 0.17 14.7 number of piglets weaned Pig weaning12.0 0.1 0.88 11.8 12.1 0.4 0.53 13.0 weight, lb Litter 168.6 3.0 0.34162.9 178.8 8.4 0.19 193.1 weaning weight, lb Sow body 7.0 2.8 0.09−23.4 −21.3 7.9 0.85 −13.7 weight change, lb Wean-estrus 4.7 0.4 0.504.9 6.0 0.5 0.77 6.3 intervals

TABLE 13C Meta-analysis for feeding clay-based diets to high prolificsows for the entire gestation + lactation Parity = 4 & 5 Parity = 6 & 7therapeutic P- therapeutic P- Item Control clay PSE value Control clayPSE value # of Trials 2 2 2 2 # of Sows 35 29 27 27 Parity Total born17.1 17.5 0.3 0.35 17.0 17.9 0.3 0.05 Born alive 15.9 16.7 0.3 0.09 15.816.3 0.3 0.28 Stillborn, % 3.2 2.3 1.0 0.49 4.1 5.1 1.0 0.48 Mummies, %3.6 2.8 0.8 0.47 2.6 3.4 0.9 0.51 Stillborns + 6.8 5.0 1.3 0.32 6.7 8.61.4 0.34 Mummies, % Litter birth 45.7 44.0 1.2 0.30 41.7 43.4 1.3 0.34weight, lb Pig birth 2.90 2.71 0.07 0.05 2.65 2.72 0.07 0.52 weight, lbPre-weaning 7.3 8.8 1.7 0.60 10.0 11.6 1.7 0.59 mortality, % Total 14.614.5 0.4 0.35 15.0 13.9 0.4 0.70 number of piglets weaned Pig weaning12.5 12.2 0.3 0.37 11.5 11.5 0.3 0.99 weight, lb Litter 181.4 180.6 5.50.92 160.0 161.5 5.9 0.86 weaning weight, lb Sow body 12.8 5.2 5.0 0.2818.2 13.4 5.5 0.53 weight change, lb Wean-estrus 4.6 4.5 0.5 0.51 4.14.1 0.5 0.85 intervals

TABLE 13D Meta-analysis for feeding clay-based diets to high prolificsows for the entire gestation + lactation Parity ≥ 8 P- therapeutic P-Item value Control clay PSE value # of Trials 2 2 # of Sows 20 28 ParityTotal born 0.05 16.4 16.4 0.4 0.93 Born alive 0.28 14.8 15.1 0.4 0.57Stillborn, % 0.48 3.5 5.5 1.1 0.21 Mummies, % 0.51 5.5 2.8 1.0 0.04Stillborns + 0.34 9.0 8.3 1.5 0.73 Mummies, % Litter birth 0.34 38.741.7 1.4 0.13 weight, lb Pig birth 0.52 2.54 2.71 0.08 0.15 weight, lbPre-weaning 0.59 12.9 12.5 1.9 0.35 mortality, % Total 0.70 14.1 12.90.4 0.27 number of piglets weaned Pig weaning 0.99 11.3 11.6 0.3 0.52weight, lb Litter 0.86 145.4 156.1 6.4 0.24 weaning weight, lb Sow body0.53 40.9 18.8 6.0 0.01 weight change, lb Wean-estrus 0.85 4.3 4.3 0.60.30 intervals

Example 7: Feeding Clay to Sows Improves Litter Size at Birth and atWeaning

The effect of feeding Clay to sows during gestation and lactation wasevaluated to determine the effect on reproductive performance. Sows(parity≥2) were randomly selected from a commercial herd were allottedto either a Control diet (CON) or a diet containing Clay at 4.0 lb/ton,resulting in 97 sows for CON and 95 sows for Clay treatment. Dietarytreatments started on day 3 after breeding and continued to the end oflactation through top-dressing clay to the basal diet (Table 14 andTable 15). Individual sow body weight was measured on the day when sowswere transferred to the farrowing crate and at weaning to calculate bodyweight change during lactation period using the formula: Sow BWChange=Wean−(PRE−(LW+LW/5.5)), where Wean=sow weight at weaning; PRE=sowpre-farrow weight; LW=litter weight, LW/5.5=estimated placental weight.Lactation length and wean to estrus interval were recorded. The numberof piglets born (alive and dead), individual pig birth weight (alive anddead), individual pig weaning weight, and the number of piglets deadduring lactation were recorded for each litter. Cross-fostering and pullof starves were allowed within 2 days after birth and only withintreatments or to the non-test litters. In addition, piglet management,including tail docking, iron injection, male piglet castration, wereperformed. Piglets' access to the sow feed was not restricted.

TABLE 14 Dietary composition of basal gestation diet ApplewoodIngredient Gestation¹, lb Ground corn 1,659.82 SBM - HI PRO 205.24 Salt12.00 Calcium Carbonate 38%/Unical S 24.99 Lime 21% Monocal 31.63AA-L-Lysine HCL 78.8% 5.21 AA-Threonine 2.09 AA-Typtophan 100% 0.32 PHY12 Optip D2000 M 0.35 NHF 5# Sow VTM w/choline 5.00 SalCURB 6.50Difusion Plus - Promote 5.00 Choice white grease 41.85 Total 2,000.00Nutrient Composition Crude Protein, % 11.09 Fat, % 4.44 Ash, % 4.88 NDF,% 6.26 ADF, % 1.79 Moisture, % 13.87 IV AA Dig, % 0.89 Particle score,unit 72.20 Calcium, % 0.81 Phosphorus, % 0.60 Ca/P Ratio 1.35 ¹Diet wasupdated December 2018/January 2019.

TABLE 15 Dietary composition of basal lactation diet ApplewoodIngredient Lactation, lb Corn - Fine Ground 1,358.40 SBM - Brewster526.26 Salt 9.50 Calcium Carbonate 38% 14.97 Phosphate - mono dical23.96 Fat - Fancy Tallow 41.30 AA-L-Lysine HCL 78.8% 8.35 Methionine-DL1.28 AA-Threonine 3.62 Tryptophan 100% 0.51 PHY12 Optip D2000 M 0.35 NHF5# Sow VTM w/ 5.00 Choline SALCURB 6.50 Total 2,000.00 Cost per ton$219.83 Nutrient, As Fed Conc Crude Protein, % 18.02 Fat, % 4.12 Ash, %4.71 Calcium, % 0.60 NDF, % 6.23 ADF, % 1.98 Moisture, % 13.55 IV AADig. % 2.28 Particle Score, unit 59.09 Phosphorus, % 0.58 Ca/P Ratio,ratio 1.03 SW NE, kcal/kg 2,350.00 Lysine, % 1.28 ¹Diet updated 22 Feb.2019.

Data was analyzed using ANOVA by the MIXED procedure of SAS. Sow/litterserved as the experimental unit. The statistical model included fixedeffect of dietary treatments and a covariate of parity. Multiplecomparisons between treatments were performed using the Tukey adjustmentoption of SAS. All results were reported as least squares means. Thesignificance level chosen was α=0.05. Treatment effect was consideredsignificant if P<0.05, whereas values between 0.05≤P≤0.10 wereconsidered as statistical trends.

Results from Table 16 suggest that sows fed clay had increased number oftotal-born pigs (P=0.15) and live born pigs (P=0.31) than the sows fedCON. Litter birth weight was greater (P=0.18) in Clay fed sows as aresult of greater litter size. Pre-weaning mortality was lower (P=0.13),with less piglets lost due to low viability (P=0.09), in Clay fed sowscompared with control fed sows. The improvement in total pigs born aliveand pre-weaning livability resulted in greater number of pigs weaned(P=0.08) from Clay fed sows.

TABLE 16 Effects of feeding clay to sows during gestation and lactationon sow reproductive performance P- Control Clay SE value # of Sows 97 95Parity¹ 5.7 6.2 0.3 0.24 Conception rate, % 99.2 98.5 N/A 0.95 Farrowingrate, % 92.3 89.2 N/A 0.79 Total born 15.1 15.7 0.5 0.15 Born alive 13.113.4 0.4 0.31 Stillborns, % 8.7 9.6 1.0 0.48 Mummies, % 5.3 5.1 0.8 0.95Litter birth weight, lb 36.5 37.8 1.2 0.18 Pig birth weight,² lb 2.742.81 0.06 0.27 Low birth weight (<1.5 lb), % 3.9 3.8 N/A 0.87 Mediumbirth weight (1.5-3.0 lb), % 55.3 53.4 N/A 0.51 High birth weight (>3.0lb), % 40.8 42.8 N/A 0.42 Pre-weaning mortality, % 6.2 4.4 1.2 0.13Piglets lost due to low viability, % 2.0 0.8 0.7 0.09 Total wean 12.212.8 0.4 0.08 Lactation length, day 19.8 19.6 0.3 0.45 Pig weaningweight,³ lb 11.5 11.6 0.2 0.95 Litter weaning weight,³ lb 138.7 145.95.7 0.21 Wean-estrus intervals, day 5.2 4.3 0.5 0.15 Sow BW prior tofarrow, lb 587 600 6 0.02 Sow BW change during lactation,^(3.4) lb 5.81.1 3.5 0.26 Sow feed intake during lactation # of Sows ADFI duringlactation, lb/day 11.1 11.7 0.5 0.62 ¹Parity was used as covariate inall analyses ²Born alive was used as covariate ³Lactation length wasused as covariate ⁴Sow BW prior to farrowing was used as covariate

Example 8: Meta-Analysis of Three Clay Sow Studies

Three experiments were conducted following the same procedure toevaluate the effects of feeding clay to sows during gestation andlactation on sow reproductive performance. In each experiment, sows(parity≥2) randomly selected from the commercial herd were allotted toeither a Control diet (CON) or a diet containing clay at 4.0 lb/ton,resulting in a total of 294 sows for CON and 302 sows for clay treatmentover three experiments. Experimental diets were fed from day 3 ofgestation and continued to the end of lactation. Data from the threeexperiments were compiled for meta-analysis using the MIXED procedure ofSAS.

Data from Table 17 suggest that feeding clay to sows during gestationand lactation improved (P<0.05) total born, born alive, and number ofpigs weaned compared to pigs fed the control diet. Litter weight atbirth and at weaning were also improved (P<0.05) as a result of improvedlitter size at birth and at weaning.

TABLE 17 Meta-analysis of three sow studies fed Clay during entiregestation and lactation Table 17. Meta-analysis of three sow studies fedClay during entire gestation and lactation Meta-analysis (by trial) % P-Item Control Clay Change PSE value # of Trials 3 3 # of Sows 294 302Parity 5.7 5.7 0.2 1.00 Total born 14.1 14.9 5.7% 0.3 0.002 Born alive12.5 13.1 4.6% 0.3 0.01 Stillborn, % 6.59 7.72 17.0% 0.67 0.03 Mummies,% 4.24 4.38 3.3% 0.57 0.74 Stillborns + 10.8 12.1 11.7% 0.9 0.07Mummies, % Litter birth 36.0 37.5 4.2% 0.8 0.02 weight, lb Pig birthweight, 2.78 2.81 1.2% 0.05 0.33 lb % of pigs with 6.8 6.0 −12.6% N/A0.12 birth weight < 1.7 lb Pre-weaning 7.1 6.6 −6.5% 0.9 0.51 mortality,% Total number of 11.5 12.2 5.5% 0.3 0.004 piglet weaned Pig weaning12.2 12.2 0.6% 0.2 0.59 weight, lb Litter weaning 139.7 147.1 5.3% 3.90.01 weight, lb Sow body 13.7 8.6 −37.7% 3.1 0.03 weight change, lbWean-estrus 4.4 4.3 −1.1% 0.4 0.85 intervals 2014-006 P- Item ControlClayt PSE value # of Trials 1 1 # of Sows 97 102 Parity 6.1 5.8 0.3 0.42Total born 14.1 14.7 0.4 0.15 Born alive 13.3 13.6 0.4 0.37 Stillborn, %3.23 4.36 0.67 0.13 Mummies, % 2.00 2.87 0.65 0.24 Stillborns + 5.2 7.21.0 0.09 Mummies, % Litter birth 38.6 39.0 1.0 0.72 weight, lb Pig birthweight, 2.94 2.91 0.05 0.63 lb % of pigs with 7.1 6.8 N/A 0.77 birthweight < 1.7 lb Pre-weaning 7.8 8.1 1.1 0.84 mortality, % Total numberof 12.2 12.5 0.3 0.39 piglet weaned Pig weaning 12.5 12.8 0.2 0.12weight, lb Litter weaning 150.5 158.2 4.1 0.09 weight, lb Sow body 9.610.9 3.9 0.77 weight change, lb Wean-estrus 4.3 4.6 0.2 0.26 intervals2017-006 P- Item Control Clayt PSE value # of Trials 1 1 # of Sows 100105 Parity 5.1 5.0 0.2 0.64 Total born 14.0 15.2 0.4 0.005 Born alive13.0 14.2 0.3 0.005 Stillborn, % 3.35 4.52 0.75 0.17 Mummies, % 2.291.92 0.57 0.55 Stillborns + 5.6 6.4 1.0 0.46 Mummies. % Litter birth39.6 42.9 1.0 0.003 weight. lb Pig birth weight, 2.99 3.08 0.05 0.12 lb% of pigs with 6.6 4.9 N/A 0.06 birth weight <1.7 lb Pre-weaning 8.4 8.61.0 0.82 mortality, % Total number of 11.9 12.9 0.3 0.007 piglet weanedPig weaning 12.0 11.8 0.2 0.43 weight, lb Litter weaning 144.6 152.3 4.60.13 weight. lb Sow body 13.3 5.3 3.4 0.04 weight change, lb Wean-estrus4.7 4.7 0.4 0.95 intervals 2019-001 P- Item Control Clayt PSE value # ofTrials 1 1 # of Sows 97 95 Parity 5.7 6.2 0.3 0.24 Total born 14.6 15.30.5 0.15 Born alive 12.8 13.2 0.4 0.31 Stillborn, % 7.76 8.51 1.09 0.48Mummies, % 4.82 4.76 0.96 0.95 Stillborns + 12.6 13.3 1.4 0.62 Mummies,% Litter birth 35.5 37.1 1.2 0.18 weight. lb Pig birth weight, 2.67 2.740.07 0.27 lb % of pigs with 6.8 6.3 N/A 0.63 birth weight < 1.7 lbPre-weaning 6.6 4.7 1.3 0.13 mortality, % Total number of 11.8 12.6 0.50.07 piglet weaned Pig weaning 11.5 11.5 0.2 0.95 weight, lb Litterweaning 136.4 144.0 6.6 0.21 weight, lb Sow body 1.1 −3.2 3.8 0.26weight change, lb Wean-estrus 5.2 4.4 0.6 0.18 intervals

Total fecal amino acid concentration was reduced (P<0.01) for sows fedclay verses control fed sows. In a review from Dai et al., (2015), theprevailing information suggests that amino acid recycling is increasedduring pregnancy, triggering improvements in fetal implantation. Theregression analyses below suggest that reduced fecal amino acid levelsenhance piglet survival post-farrowing and weight gain during lactation.Reduced amino acid levels also is indicative of reduced ammoniaproduction, which is favorable to improving embryo survival (Dai et al.,2015). Taken together these data suggest that the improved amino acidutilization of reduced fecal amino acid concentrations are related toimprovements in signaling to promote pregnancy and reduce fetal exposureto toxins like ammonia and nitric oxide. Sows fed clay had improvedamino acid utilization further reducing the exposure to the toxiceffects of high ammonia production. The data in Table 18 furthersuggests that short chain fatty acid concentrations are reduced in thefeces of clay fed sows. Dai (2015) further suggests that reduced shortchain fatty acids improves insulin sensitivity, which is related toimproved fetal survival and post weaning development.

TABLE 18 Metabolites in sow feces (end of gestation) P- % Item ControlClay SE value change # of sows analyzed for fecal 16 16 metabolitesParity 5.75 6.31 0.66 0.55 Reproductive performance of sampling sowsTotal born 15.2 16.1 0.7 0.34 Born alive 12.6 13.6 0.7 0.34 Pig birthweight, lb 3.0 3.0 0.1 0.90 PWM. % 8.7 4.9 2.7 0.32 Total wean 12.2 12.90.7 0.53 Pig wean weight. lb 11.6 12.1 0.5 0.45 Sow fecal metabolitesend of gestation¹ Fatty acids in feces. mg/g acetic acid 4.58 3.28 0.490.09 −28% propionic acid 3.69 2.46 0.45 0.07 −33% butyric acid 1.99 1.270.25 0.07 −36% valeric acid 0.586 0.375 0.072 0.06 −36% isovaleric acid0.173 0.128 0.020 0.13 −26% Total SCFA 11.00 7.53 1.23 0.07 −32% C6:00.019 0.014 0.006 0.54 −26% C8:0 0.0059 0.0056 0.0005 0.67  −5% C14:00.125 0.127 0.018 0.93  2% C15:0 0.090 0.178 0.027 0.01  98% C16:0 0.8811.086 0.075 0.08  23% C16:1 0.017 0.013 0.001 0.08 −22% C18:0 0.3360.451 0.028 0.009  34% C18:1 0.606 0.723 0.113 0.47  19% Bile acids infeces. ug/g Cholic acid 9.52 9.48 0.20 0.88  0% Chenodeoxycholic acid0.64 0.66 0.13 0.92  3% Lithocholic acid 870 413 104 0.007 −52%Hyodeoxycholic acid 1311 240 178 0.001 −82% Total bile acids 2153 719246 0.001 −67% Amino acids in feces. ug/g Alanine 161 50 17 0.0007 −69%Arginine 26.0 10.0 6.3 <.0001 −61% Asparagine 2.46 1.63 1.14 0.01 −34%Aspartic acid 35.6 47.8 5.5 0.14  34% Citrulline 47.7 37.1 6.1 0.22 −22%Glutamic acid 564 461 68 0.29 −18% Glutamine 9.87 7.83 0.48 0.01 −21%Glycine 41.0 27.3 8.9 0.07 −33% Histidine 8.41 8.06 0.57 0.67  −4%Leucine/Isoleucine 77.9 22.2 7.6 0.0001 −71% Lysine 85.5 70.4 8.2 0.21−18% Methionine 23.8 11.8 2.5 0.005 −50% Ornithine 6.40 7.61 1.05 0.43 19% Phenylalanine 92.3 9.3 11.3 0.0001 −90% Proline 41.8 14.7 5.8 0.005−65% r-amino-n-butyric acid 5.1 12.3 3.2 0.004 141% Serine 56.5 38.0 4.90.02 −33% Taurine 1.83 0.31 0.58 0.08 −83% Threonine 42.9 22.0 3.20.0004 −49% Tryptophan 7.9 2.7 1.0 0.002 −65% Tyrosine 73.0 11.7 9.60.0005 −84% Valine 77.1 27.5 8.8 0.001 −64% Total amino acids 1490 935142 0.01 −37%

Linear Regression Analysis to Build Prediction Equation for PWM and PigWeaning Wt Pig Weaning Weight was Predicted Using the FollowingEquation:

Pig weaning weight (Control)=a ₂₋₁₁×Parity(2-11)+1.123×weaningage−0.00083×Total AA in sow feces end of gestation (μg/g)−0.0215×birthweight (lb)−11.945

Pig weaning weight (clay)=a ₂₋₁₁×Parity(2-11)+1.123×weaningage−0.00201×Total AA in sow feces end of gestation (μg/g)+3.342×birthweight (lb)−19.626

R ²=0.82

This equation suggests that the total AA concentration in sow fecescollected at the end of gestation had negative correlation with pigweaning weight in both treatments. Pig weaning weight from sows fed clayhad (0.00201−0.00083)/0.00083=142% greater impact from total AAconcentration in sow feces compared with Control.

Pre-Weaning Mortality was Predicted Using the Following Equation:

Pre-weaning mortality (Control)=a ₂₋₁₁×Parity (2-11)+1.323×Total SCFA insow feces−10.601

Pre-weaning mortality (clay)=a ₂₋₁₁×Parity (2-11)+0.337×Total SCFA insow feces−1.463

R ²=0.59

This equation suggests that the total SCFA concentration in sow fecescollected at the end of gestation had positive correlation with pig PWMin both treatments. Pig PWM from sows fed day had(1.323−0.337)/1.323=75% less impact from total SCFA concentration in sowfeces compared with Control.

Example 9: Feeding Clay to Sows Improved Concentration of TotalImmunoglobins in their Offspring

The immunocrit measures total immunoglobulins in blood, which is theprotein that recognizes bacteria and other agents that can causediseases. When piglets are born, they have very little immunoglobulinconcentration (essentially zero). Thus, all the immunoglobulin in bloodfrom a newborn piglet comes from the sow by way of colostrum intake.Therefore, the immunocrit measure can determine if a piglet has receivedenough colostrum. Previous results have indicated that an immunocritvalue at birth below 0.05 is associated with greater risk of preweaningmortality due to insufficient colostrum intake. In this experiment, atotal of 37 piglets from sows fed a control diet and 50 piglets fromsows fed a diet containing Clay at 4.0 lb/ton during gestation andlactation were used to evaluate the immunocrit values on day 2 afterbirth and at weaning.

Results from Table 19 show that piglets from sows fed Clay had 5.9%greater immunocrit value on day 2 after birth (P=0.44) compared withpiglets from sows fed control diet. Approximately 44% less pigs fromsows fed Clay with immunocrit<0.05 at birth suggest a greater colostrumintake and higher immunoglobins concentration compared with pigs fromsows fed control diet. In addition, the greater immunocrit value atweaning (7.0% increase) in a litter from sows fed Clay indicate a betterimmune status and potentially better health status and growthperformance in later growing phases after weaning.

TABLE 19 Immunocrit values of piglets from sows fed Control diet anddiet containing Clay at 4.0 lb/ton P- % Change over Item Control Clay SEvalue Control Piglet Immunocrit # of pigs measured 37 50 # of littersmeasured 20 25 Immunocrit on Day 2 0.095 0.101 0.005 0.44 +5.9% afterbirth % of pigs with 10.8 6.0 N/A 0.43  −44% Immunocrit <0.05 Immunocritat 0.040 0.043 0.002 0.25 +7.0% weaning

Example 10: Feeding Clay to Sows Improved Livability of their Offspringfrom Birth to Market

A study was conducted to evaluate the effects of feeding Clay to sowsduring gestation and lactation on livability of their offspring frombirth to market. A total of 352 pigs from sows fed a control diet and143 pigs from sows fed Clay at 4.0 lb/ton were individually identifiedusing ear tags and tracked from nursery to market. Removal rate fromnursery to market, and percentage of light pigs were lower (P=0.88 andP=0.06, respectively) in pigs from sows fed Clay, resulting in more pigsmarketed at the primary market compared with pigs from sows fed controldiet (93.0 vs. 88.6%; Table 20). Taken together the data shown inExample 1, feeding Clay to sows resulted in 0.6 more pigs per litter atweaning and 1.1 more pigs per litter marketed at the primary market dueto greater livability from birth to market compared with pigs fedcontrol diet.

TABLE 20 Birth to market livability of piglets from sows fed Controldiet and diet containing Clay Sow Treatment Control Clay P-value Nurseryphase # of pigs start 352 143 Mortality, % 0.85 0.70 0.58 Removal(mortality + 6.5 4.9 0.75 fallbacks), % Grow-finish phase Mortality, %2.3 2.1 0.84 Nursery to market Removal (mortality + 8.8 7.0 0.88fallbacks), % Light + Junk pigs, % 2.6 0.0 0.06 Pigs to the primarymarket, % 88.6 93.0 0.97 Birth to market Total born/litter 15.1 15.70.15 Born alive/litter 13.1 13.4 0.31 Total wean/litter 12.2 12.8 0.08Pigs to the primary market/litter 10.8 11.9

1. A method of improving reproductive and litter performance of amaternal animal, the method comprising, orally administering to theanimal an effective amount of a therapeutic clay.
 2. The method of claim1, wherein the animal is a pig.
 3. The method of claim 1, wherein theclay is formulated in a feed composition for oral administration to theanimal.
 4. The method of claim 1, wherein the clay is administeredduring gestation, during lactation, and combinations thereof.
 5. Themethod of claim 1, wherein the clay is administered for a period of timeduring gestation.
 6. The method of claim 1, wherein the clay isadministered from breeding until farrowing.
 7. The method of claim 1,wherein the clay is administered for a period of time during lactation.8. The method of claim 1, wherein the clay is administered fromfarrowing until weaning.
 9. The method of claim 1, wherein improvingreproductive performance comprises reducing embryonic loss, increasinglitter size, increasing the number of live births, improving the immunestatus of the maternal animal, reducing the concentration of maternalfecal amino acids, reducing the concentration of maternal fecalshort-chained amino acid, and increasing litter birth weight.
 10. Themethod of claim 9, wherein improving the immune status of the maternalanimal comprises an increased level of IFNγ and TNF-α in the maternalanimal, and decreased levels of TRAIL in the maternal animal.
 11. Themethod of claim 10, wherein the level of pre-farrowing TNF-α in thematernal animal is positively correlated with total wean, negativelycorrelated with subsequent stillborns, and positively correlated withsubsequent mummies.
 12. The method of claim 10, wherein the level ofpre-farrowing TRAIL is negatively correlated with subsequent total bornand subsequent born alive.
 13. The method of claim 10, wherein the levelof wean IFN-γ is positively correlated with total wean.
 14. The methodof claim 1, wherein improving litter performance comprises increasingamount of young animal colostrum intake, reducing young animalpre-weaning mortality, reducing the number of young animals lost due tolow viability, reducing the number of weaned young animals, improvingthe immune status of young animals at weaning, reducing the number oflightweight young animals from nursery to market, increasing the numberof young animals marketed per sow, and increasing calculated litterweight gain.
 15. The method of claim 1, wherein the animal is a pig. 16.The method of claim 15, wherein the amount of clay in a feed compositionranges from about 0.1 lb/ton to 10 lb/ton.
 17. The method of claim 15,wherein the amount of clay in a gestation feed composition ranges fromabout 0.5 lb/ton to 4.0 lb/ton.
 18. The method of claim 15, wherein theamount of clay in a lactation feed composition ranges from about 0.5lb/ton to 1.5 lb/ton.
 19. The method of claim 15, wherein the amount ofclay administered to a sow ranges from about 1.0 g/d to about 10 g/d.20. The method of claim 15, wherein the amount of clay administered toan animal ranges from about 0.1 g/d to about 8 g/d. 21.-29. (canceled)